The DOI matches its Crossref record; 187 of the 187 references it cites were found in a registry or an index; 160 of the 370 sources its claims cite were checked for support.
Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8
Open accessAbstract
Triglyceride-rich lipoproteins deliver fatty acids to tissues for oxidation and for storage. Release of fatty acids from circulating lipoprotein triglycerides is carried out by lipoprotein lipase (LPL), thus LPL serves as a critical gatekeeper of fatty acid uptake into tissues. LPL activity is regulated by a number of extracellular proteins including three members of the angiopoietin-like family of proteins. In this review, we discuss our current understanding of how, where, and when ANGPTL3, ANGPTL4, and ANGPTL8 regulate lipoprotein lipase activity, with a particular emphasis on how these proteins interact with each other to coordinate triglyceride metabolism and fat partitioning.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review synthesizes how ANGPTL3, ANGPTL4, and ANGPTL8 regulate lipoprotein lipase (LPL) and triglyceride partitioning across fasting, feeding, thermogenesis, and disease. It updates the A3-4-8 model, emphasizing that ANGPTL3-ANGPTL8 complexes are the key endocrine inhibitor of LPL in oxidative tissues, while adipose ANGPTL4 acts locally during fasting and is suppressed by ANGPTL8 in the fed state.
Key findings
- ANGPTL4 is fasting-induced in adipose tissue and inhibits LPL locally, reducing triglyceride uptake into adipose; adipose-specific ANGPTL4 knockout increases adipose LPL activity but not other tissues.
- ANGPTL8 does not inhibit LPL on its own; it forms a complex with ANGPTL3 with apparent stoichiometry of 3 ANGPTL3:1 ANGPTL8, and this complex inhibits LPL far more potently than either protein alone.
- ANGPTL8 also binds ANGPTL4 (apparent 1:1 stoichiometry), but ANGPTL4-ANGPTL8 complexes are substantially poorer at inhibiting LPL than ANGPTL4 alone, suggesting ANGPTL8 suppresses ANGPTL4 inhibition during feeding.
- Therapeutic targeting data cited: Evinacumab lowered triglycerides by 76%, LDL-cholesterol by 23.2%, and HDL-cholesterol by 18.4% in healthy individuals; Vupanorsen was associated with a 33%–63% decrease in triglycerides.
Methods
- Narrative review of published animal models (Table 1) and human genetic studies on ANGPTL3, ANGPTL4, and ANGPTL8 in lipoprotein metabolism.
- Synthesizes mechanistic, physiological, and therapeutic literature to revisit the 2016 A3-4-8 model of LPL regulation across fasted, fed, thermogenic, and high-fat-diet/obesity states.
- No new primary data, systematic search strategy, or meta-analysis are reported.
Limitations
- Stated: the mechanism by which ANGPTL3-ANGPTL8 complexes inhibit LPL remains unresolved; the structural basis for ANGPTL8’s opposite effects on ANGPTL3 and ANGPTL4 is unknown, and only C-terminal fibrinogen domains of ANGPTL3/ANGPTL4 have been solved.
- Stated: many metabolic states are understudied, including exercise, starvation, chronic inflammation, aging, and chronic high-fat feeding; whether ANGPTL-regulated partitioning shifts occur in obesity is unclear.
- Evident: as a narrative review, it does not systematically assess bias or study quality, and several conclusions depend on cited in vitro studies that may use supraphysiological ANGPTL3 concentrations or lack ANGPTL8.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
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Verification
Claims the paper makes
89 Not checked yet · 39 Partly supported · 27 No full text of the sources · 23 Own interpretation · 22 Supported · 11 Supported so far · 3 Not supported · 2 No basis given · 1 Mixed support · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Peritoneal macrophages isolated from ANGPTL4-deficient mice exhibit significantly more lipid uptake and inflammatory cytokine release than those from normal mice when incubated with chyle (chylomicron-containing lymphatic fluid) (59).”
What the sources say
- Disputedcites [59] sourceExperimental — accuracy not yet measured
In Results, under “Absence of Angptl4 stimulates foam cell formation and inflammation in MLN-resident macrophages” (page unavailable), the paper explicitly reports no clear difference in foam-cell formation between wild-type and Angptl4-deficient peritoneal macrophages loaded with chyle, contrary to the claimed greater lipid uptake. It reports chyle-induced inflammatory gene expression, but the cited passages do not establish greater cytokine release from deficient cells than from wild-type cells. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“and most of the studies showing that ANGPTL3-mediated LPL inhibition in vitro required supraphysiological concentrations of ANGPTL3 to achieve significant inhibition (60, 105, 107, 115).”
What the sources say
- Partly supportedcites [60] sourceExperimental — accuracy not yet measured
The in vitro results (section “Soluble mouse GPIHBP1 stabilizes but does not activate LPL”; page unavailable) show substantial LPL inhibition with 500 nM ANGPTL3. The paper does not compare that concentration with physiological ANGPTL3 levels or establish that most studies required supraphysiological concentrations. (LLM, conf=0.81)
- Disputedcites [105] sourceExperimental — accuracy not yet measured
The Results report substantial in-vitro LPL inhibition at 10 µg/ml. But the Discussion explicitly says that the estimated ANGPTL3 concentration in normal humans is close to the dose required for in-vitro inhibition and suggests that ANGPTL3 may act physiologically. That contradicts attributing to this paper the conclusion that supraphysiological concentrations were required. (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
- Partly supportedcites [107] sourceExperimental — accuracy not yet measured
The Results section reports that recombinant ANGPTL3 inhibited LPL in vitro, while a mutant N-terminal fragment inhibited it only at high concentrations (page unavailable). The paper does not establish that those concentrations were supraphysiological or that high concentrations were required for significant inhibition by unmodified ANGPTL3. (LLM, conf=0.84)
- Supportedcites [115] source
The Discussion states that biochemical studies found ANGPTL3 could inhibit LPL in vitro, but each required supraphysiological ANGPTL3 concentrations. It also says the authors' own experiments required high concentrations. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“It is important to note that ANGPTL proteins are likely not the primary driver of the alterations in lipid partitioning that occur during thermogenesis.”
What the sources say
- Disputedcites [71] sourceExperimental — accuracy not yet measured
The Discussion describes ANGPTL4 as having a “major role” in lipid partitioning during sustained cold and as a “master regulator” of tissue LPL activity and fatty-acid uptake. That directly conflicts with the claim that ANGPTL proteins are likely not a primary driver in this thermogenic setting. (LLM, conf=0.89)
Checked by a reasoning model — may be wrong.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“ANGPTL4 loss-of-function mutations in humans are associated with lower plasma triglycerides (40, 56–58).”
What the sources say
- Not checked yetcites [40] source
Checked before — its earlier verdict is held back until a new check runs.
- Supportedcites [56] source
The Results section (‘Inactivating Mutations in ANGPTL4,’ Association with Lipid Levels) reports that human carriers of inactivating ANGPTL4 mutations had significantly lower triglyceride levels than noncarriers. It also reports lower levels among carriers of the E40K variant. (LLM, conf=0.95)
- Supportedcites [57] source
The section “ANGPTL4 Loss-of-Function Mutations, Plasma Lipid Levels, and Coronary Artery Disease” reports significantly lower triglyceride levels in human carriers of loss-of-function alleles than in noncarriers (35% lower on average; P = 0.003). The Discussion states the same association. (LLM, conf=0.95)
- Supportedcites [58] source
The Abstract reports that ANGPTL4 variants were more frequent in people in the lowest triglyceride quartile and identifies four variants in that group predicted to truncate the protein or disrupt splicing. It also reports lower plasma triglycerides in carriers of the E40K variant across three populations. These passages support the claimed association in humans. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not checked yet
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In adipocytes, ANGPTL4 appears able to inactivate LPL both intracellularly (64, 65) and extracellularly (29, 66).”
What the sources say
- Supportedcites [64] source
This source is cited for the intracellular part of the sentence; separate citations accompany the extracellular part. Its Discussion states that ANGPTL4 promotes intracellular degradation of LPL in adipocytes, and its conclusion says ANGPTL4 interacts with LPL inside adipocytes. (LLM, conf=0.94)
- Supportedcites [65] source
This citation is attached to the intracellular part of the sentence; separate citations accompany the extracellular part. The Abstract concludes that ANGPTL4 promotes intracellular cleavage of LPL in adipocytes, and the section ‘ANGPTL4 promotes the intracellular cleavage of LPL’ says this supports an intracellular mode of action. (LLM, conf=0.93)
- Partly supportedcites [29] sourceExperimental — accuracy not yet measured
The Results show that ANGPTL4 inhibits LPL in an in-vitro assay and that an antibody can rescue LPL activity, supporting the cited extracellular aspect. The paper does not establish that this occurs in adipocytes; the intracellular aspect is attributed to other citations. (LLM, conf=0.83)
- Not checked — no full text of the sourcecites [66] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Studies with knockout mice confirm that in the absence of ANGPTL4, LPL activity and TG uptake in adipose increases under fasting conditions (31, 32, 63).”
What the sources say
- Not checked yetcites [31] source
- Not checked yetcites [32] source
- Supportedcites [63] source
The Abstract’s Results state that fasted Angptl4−/− mice had increased adipose LPL activity and triglyceride uptake compared with wild-type mice. The Results section on adipose lipase activity also reports greater lipase activity in fasted knockout mice, consistent with increased triglyceride uptake. (LLM, conf=0.94)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Consistent with a role for ANGPTL4 in thermogenic triglyceride partitioning, either whole body or BAT-specific deletion of ANGPTL4 resulted in increased LPL activity and triglyceride uptake in BAT (33, 71).”
What the sources say
- Partly supportedcites [33] sourceExperimental — accuracy not yet measured
The Results section (‘Genetic loss of ANGPTL4 in brown adipocytes…’, page unavailable) reports increased LPL activity and greater tracer-labeled lipid uptake in BAT after BAT-specific ANGPTL4 deletion. This paper does not report the same paired findings from its own whole-body deletion experiment, so it supports the BAT-specific part of the sentence but not the whole-body part. (LLM, conf=0.85)
- Partly supportedcites [71] sourceExperimental — accuracy not yet measured
The Results sections on BAT LPL activity and TRL-derived fatty-acid uptake report higher BAT LPL activity and a gradient of uptake across whole-body Angptl4 knockout, wild-type, and overexpressing mice. The Methods (Mice) describe whole-body Angptl4 knockout mice, not BAT-specific deletion; this paper therefore does not support that part of the claim. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Cold exposure induces large increases in triglyceride uptake into brown adipose tissue (BAT) (68, 69).”
What the sources say
- Not checked — no full text of the sourcecites [68] source
- Supportedcites [69] source
The Results section, “Cold exposure enhances lipolysis-mediated FA uptake from TRL-mimicking particles by BAT,” reports that 24 hours at 7°C increased BAT uptake of triglyceride-derived label by 111–150% compared with 21°C. The uptake was mainly of fatty acids liberated by lipolysis, rather than intact triglyceride-rich particles. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Angptl4 gene expression decreases in brown adipose tissue in the cold (33, 70, 71).”
What the sources say
- Supportedcites [33] source
The Results section reports that acute cold exposure caused a marked reduction in Angptl4 mRNA in brown adipose tissue. Figure 3A compares BAT from mice exposed to 4 °C or room temperature for four hours. (LLM, conf=0.95)
- Not checked — no full text of the sourcecites [70] source
- Partly supportedcites [71] sourceExperimental — accuracy not yet measured
The Results section, under “ANGPTL4 expression in BAT is down-regulated upon sustained cold exposure,” reports reduced Angptl4 mRNA in brown adipose tissue after 10 days of cold exposure. The claim omits that duration qualifier: the same passage says one day of cold exposure did not affect expression. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the years since, multiple laboratories have confirmed the ability of ANGPTL4 to inhibit LPL (49–55).”
What the sources say
- Supportedcites [49] source
The Results report that adding ANGPTL4 caused a dramatic decline in LPL activity in both the medium and the cell-bound fraction. This paper therefore supports its role as one of the cited laboratory confirmations of ANGPTL4-mediated LPL inhibition. (LLM, conf=0.92)
- Could not verifycites [50] sourceExperimental — accuracy not yet measured
The indexed copy returns bibliographic material, including a title about inhibition of LPL- and HL-dependent hepatic cholesterol uptake, but no passage stating that ANGPTL4 inhibits LPL itself. Searches for ANGPTL4 inhibiting LPL and for lipoprotein lipase did not retrieve a decisive passage from the paper's body. (LLM, conf=0.70)
- Supportedcites [51] source
The Introduction describes ANGPTL4 as a potent inhibitor of LPL in vitro. The Results report that ANGPTL4 reduced LPL activity, while the Discussion describes inhibitory findings from both this study and earlier studies by Sukonina et al. and Lafferty et al. The studies differ on the mechanism, not on ANGPTL4’s ability to inhibit LPL. (LLM, conf=0.92)
- Supportedcites [52] source
The Introduction describes earlier studies by Sukonina et al. and Lafferty et al. that reported ANGPTL4 inhibition of LPL, while noting disagreement about the mechanism. The Discussion reports this paper’s own experimental evidence of inhibition. Together, these passages support the claim that multiple laboratories confirmed ANGPTL4’s ability to inhibit LPL. (LLM, conf=0.90)
- Supportedcites [53] source
The Results report dose-dependent inhibition of LPL by ANGPTL4, and the Discussion states that the authors demonstrated ANGPTL4 inhibition through several methods. The introduction also describes earlier studies of ANGPTL4’s effects on LPL, supporting the statement that this ability had been confirmed beyond this laboratory. (LLM, conf=0.89)
- Supportedcites [54] source
The Results section reports that ANGPTL4 inhibited LPL in an activity assay (Fig. 5B), confirming the finding for which this paper is cited. The phrase “multiple laboratories” refers to the cited studies collectively, not to a claim that this paper tested results from multiple laboratories. (LLM, conf=0.92)
- Supportedcites [55] source
The Results report that ANGPTL4 lowered LPL activity in a dose-dependent manner and rapidly inactivated LPL during preincubation. This paper therefore supplies one of the cited confirmations of ANGPTL4’s inhibitory ability; the group of citations, rather than this paper alone, supports the reference to multiple laboratories. (LLM, conf=0.91)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
- Probably not a substantial claim. 24
- It may state two separate claims as one. 74
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“This mechanism has not yet been universally accepted and studies from the laboratory of Saskia Neher have suggested that ANGPTL4 acts as a reversible, uncompetitive inhibitor of LPL (53, 100).”
What the sources say
- Disputedcites [53] sourceExperimental — accuracy not yet measured
The Discussion states that ANGPTL4 inhibits LPL reversibly, but identifies the kinetic mechanism as noncompetitive, not uncompetitive. The paper’s Conclusion makes the same distinction, directly contradicting the cited sentence’s description of the mechanism. (LLM, conf=0.92)
Checked by a reasoning model — may be wrong.
- Disputedcites [100] sourceExperimental — accuracy not yet measured
The Discussion supports reversible inhibition but explicitly calls ANGPTL4 a noncompetitive inhibitor, not an uncompetitive one. The Results likewise identify its inhibition of LPL on VLDL as pure noncompetitive inhibition. No page numbers are provided in our copy. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Disputed
Every source the paper cites for this claim was checked and supports it.
In the paper
“In 2000, two groups described the discovery of a secreted PPAR target gene expressed highly in adipose tissue (46, 47).”
What the sources say
- Supportedcites [46] source
The Abstract reports the isolation of a novel PPAR target gene encoding secreted FIAF and says it is predominantly expressed in adipose tissue. The Discussion likewise describes the factor as primarily secreted from adipose tissue and its expression as stimulated by PPARs. (LLM, conf=0.94)
- Supportedcites [47] source
The paper’s opening summary describes the isolation of PGAR as a PPARγ target gene encoding a secreted angiopoietin-related protein and says its expression is predominantly localized to adipose tissue and placenta. The Results describe the cloning strategy used to identify the novel gene. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“It is important to note, however, that modulation of ANGPTL4 expression is not essential for cold-induced thermogenesis or even cold-induced changes in triglyceride partitioning.”
What the sources say
- Supportedcites [71] source
The Results section on BAT LPL activity reports similar cold-induced body-temperature and thermogenic-gene responses across Angptl4 genotypes. The Discussion reports a modest cold-induced increase in BAT LPL activity and triglyceride-rich-lipoprotein-derived fatty-acid uptake even in Angptl4-knockout mice. Thus ANGPTL4 modulation is not essential for these responses, although the paper emphasizes its major role in regulating lipid partitioning. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Like angiopoietin proteins, ANGPTL proteins, with the exception of ANGPTL8, contain a coiled-coil domain and a large globular C-terminal fibrinogen-like domain (12, 13).”
What the sources say
- Not checked — no full text of the sourcecites [12] source
- Partly supportedcites [13] sourceExperimental — accuracy not yet measured
The Angiopoietin-Like Proteins section states that ANGPTLs have an amino-terminal coiled-coil domain and a carboxy-terminal fibrinogen-like domain, except that ANGPTL8 lacks the latter. It does not describe that domain as large or globular, so those specific descriptors are not verified by our copy. (LLM, conf=0.84)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Every source the paper cites for this claim was checked and supports it.
In the paper
“These data suggested a model in which ANGPTL4 is induced in nonexercising skeletal muscle to prevent lipotoxicity and to divert fuel to exercising muscle where fatty acid oxidation is increased (73).”
What the sources say
- Supportedcites [73] source
The Discussion’s proposed model (Fig. 7) says ANGPTL4 induction in nonexercising muscle reduces fatty-acid uptake, likely preventing lipid overload. It also says maintained LPL activity in exercising muscle makes those fatty acids available for oxidation. The citing sentence appropriately describes this as a suggested model. (LLM, conf=0.94)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The family currently has eight known members, ANGPTL1-8, with pleiotropic functions (13).”
What the sources say
- Supportedcites [13] source
The Angiopoietin-Like Proteins section states that eight members, ANGPTL1 through ANGPTL8, had been discovered. The Conclusion says that some ANGPTL proteins exhibit pleiotropic effects across several biological functions, supporting the family-level description. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“GPIHBP1 also anchors LPL to the capillary wall during lipolysis of lipoproteins (8, 9).”
What the sources say
- Supportedcites [8] source
The Discussion reports that GPIHBP1 is located on the luminal face of capillary endothelium, binds LpL, and serves as a platform for LpL-mediated processing of chylomicrons. This supports the claim that it anchors LpL at the capillary wall during lipolysis. (LLM, conf=0.90)
- Not checked yetcites [9] source
Checked before — its earlier verdict is held back until a new check runs.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“EL belongs to the same lipase family as LPL, but targets phospholipids on the shell of high-density lipoproteins (HDL), leading to decreased HDL levels (119–122).”
What the sources say
- Not checked — no full text of the sourcecites [119] source
- Partly supportedcites [120] sourceExperimental — accuracy not yet measured
The Abstract identifies EL and LPL as members of the same vascular lipase family and says EL has substantially greater phospholipase activity. The Results and Discussion report higher HDL cholesterol when EL is absent in mice. Our copy does not establish that EL specifically targets phospholipids on the HDL shell or that this action causes the decrease in HDL levels. (LLM, conf=0.85)
- Partly supportedcites [121] sourceExperimental — accuracy not yet measured
The Abstract identifies EL and LPL as members of the same lipase family, and the Discussion reports that EL hydrolyzes HDL lipids and likely acts at least partly through phospholipase activity. The Discussion also reports that EL expression depleted plasma HDL in mice, but says its physiological role remains unclear; it does not establish that phospholipid hydrolysis causes the decrease in HDL levels generally. Page numbers are unavailable in our copy. (LLM, conf=0.84)
- Partly supportedcites [122] sourceExperimental — accuracy not yet measured
The Results report that hepatic EL overexpression markedly reduced plasma phospholipids, while the Discussion concludes that it produced markedly low HDL levels in mice. Our copy also describes EL as a phospholipase that preferentially hydrolyzes HDL lipids, but it does not establish that EL belongs to the same lipase family as LPL or specify that it targets phospholipids on the HDL shell. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“The microbiota have also been implicated in the improved glucose tolerance observed in ANGPTL4-deficient mice fed a diet high in unsaturated fat (84).”
What the sources say
- Supportedcites [84] source
The Discussion states that ANGPTL4-deficient mice fed a diet rich in unsaturated fatty acids had improved glucose tolerance and suggests that the effect is partly dependent on the gut microbiota. In Results, suppressing gut bacteria with antibiotics substantially reduced the glucose-tolerance difference between deficient and wild-type mice. (LLM, conf=0.94)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Several studies have shown that not only is the N-terminal region of ANGPTL4 necessary and sufficient for LPL inhibition, but also that, once cleaved from the fibrinogen-like domain, the N-terminal region inhibits LPL more efficiently than full-length ANGPTL4 (49, 51, 72, 89, 90).”
What the sources say
- Partly supportedcites [49] sourceExperimental — accuracy not yet measured
The Results and Discussion (page not provided) show that the isolated N-terminal coiled-coil domain inhibits LPL, supporting sufficiency. The paper does not establish that this domain is necessary, or that cleavage makes it more efficient than full-length ANGPTL4. (LLM, conf=0.86)
- Supportedcites [51] source
The Results (page not supplied) state that the N-terminal coiled-coil domain is necessary and sufficient for LPL inhibition in vitro. The authors also report that, at equivalent amounts, the N-terminal fragment inactivated LPL more effectively than cleavage-resistant full-length ANGPTL4, both in solution and when LPL was bound to GPIHBP1. (LLM, conf=0.94)
- Partly supportedcites [72] sourceExperimental — accuracy not yet measured
In “The coiled-coil domain of Angptl4 inhibits LPL activity expressed in C2C12 cells” (page unavailable), the N-terminal domain and full-length ANGPTL4 inhibit LPL activity, while the C-terminal domain does not. This supports the N-terminal region’s sufficiency and the tested domain comparison, but the paper does not show that cleavage makes the N-terminal region more efficient than full-length ANGPTL4. (LLM, conf=0.87)
- Partly supportedcites [89] sourceExperimental — accuracy not yet measured
The introductory passage (page not available in our copy) states that the N-terminal region is necessary and sufficient for LPL inhibition. The Results report that medium containing cleavage-defective ANGPTL4 inhibited LPL less effectively than medium containing wild-type protein, but do not directly compare the isolated N-terminal region with full-length ANGPTL4. The Discussion also says cleavage is not required for inhibition, so the claimed greater efficiency of the cleaved region is not established by this paper. (LLM, conf=0.86)
- Supportedcites [90] source
The Discussion (page not provided) says only ANGPTL4 fragments containing the N terminus inhibit LPL and that cleavage generates more potent inhibitors in vitro. Figure 5 compares the isolated N-terminal fragment with cleavage-resistant full-length ANGPTL4, supporting the stated comparison. (LLM, conf=0.90)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Indeed, a recent series of studies from the laboratory of Michael Ploug have shown that ANGPTL4 can act on monomeric LPL, and that ANGPTL4 increases the inherent instability of LPL resulting in the unfolding of LPL’s catalytic domain (52, 97, 98).”
What the sources say
- Partly supportedcites [52] sourceExperimental — accuracy not yet measured
The Discussion (page not available) says ANGPTL4 accelerates LPL’s spontaneous unfolding and induces unfolding of its hydrolase domain. It does not establish that ANGPTL4 acts on monomeric LPL: the Discussion explicitly says it is unclear whether the relevant folding intermediate is part of an LPL homodimer or a dissociated monomer. (LLM, conf=0.89)
- Not checked — no full text of the sourcecites [97] source
- Supportedcites [98] source
The introductory passage states that ANGPTL4 unfolds catalytically active LPL monomers rather than dissociating LPL dimers. The Discussion reports that LPL’s hydrolase domain is borderline stable at body temperature and that ANGPTL4 binding lowers its thermal stability, leading to irreversible unfolding and inactivation. Page numbers are not provided in our copy. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“ANGPTL3 null mice have decreased cholesterol and triglyceride levels and increased LPL activity in postheparin plasma (16, 18, 106).”
What the sources say
- Not checked — no full text of the sourcecites [16] source
- Supportedcites [18] source
The Anatomical analysis and plasma lipid profile section reports markedly decreased plasma triglyceride and total cholesterol concentrations in Angptl3-null mice compared with wild-type mice. The In vivo triglyceride metabolism section reports significantly increased LPL activity in post-heparin plasma (1.57 times wild-type activity). (LLM, conf=0.95)
- Supportedcites [106] source
The Results report lower plasma triglyceride and cholesterol levels in Angptl3−/− mice. They also report that postheparin plasma LPL activity increased with refeeding in knockout mice but fell in wild-type mice; the LPL finding is specifically under refeeding conditions. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“ANGPTL4 is robustly expressed in the liver in mice, and in humans liver is the tissue with greatest ANGPTL4 expression (86, 87).”
What the sources say
- Could not verifycites [86] sourceExperimental — accuracy not yet measured
The available indexed passages are bibliographic metadata, with no paper section or page addressing tissue-specific ANGPTL4 expression. Searches for liver expression in mice and for the tissue with greatest expression in humans returned no relevant passage; the decisive article text appears to be missing from our copy. (LLM, conf=0.70)
- Partly supportedcites [87] sourceExperimental — accuracy not yet measured
The Results (page not provided) report that liver had the highest ANGPTL4 expression among the human tissues tested, supporting the human portion of the claim. Our copy does not establish robust ANGPTL4 expression in mouse liver; its mouse-related passages concern transgenic mice and cultured cells, not liver expression. (LLM, conf=0.85)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“Soon after, Shimizugawa et al. (105) made a direct connection between ANGPTL3 and LPL, finding that the KK/San mice had increased clearance of triglyceride-rich lipoproteins and showing that ANGPTL3 could inhibit LPL in vitro.”
What the sources say
- Supportedcites [105] source
The Results report enhanced clearance of VLDL triglycerides in KK/San mice, primarily through lipolysis rather than whole-particle uptake. The same section reports that recombinant ANGPTL3 inhibited LPL activity in vitro. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“LPL’s endothelial cell receptor GPIHBP1 protects LPL from ANGPTL3 inhibition as does heparin (60, 115).”
What the sources say
- Supportedcites [60] source
The results accompanying Fig. 5 report that LPL stabilized by soluble GPIHBP1 resisted ANGPTL3 inhibition, while ANGPTL3 was less effective against heparin-stabilized LPL than against unstabilized LPL. The paper therefore supports protection by both, though GPIHBP1 protected more strongly. Page numbers are not provided in our copy. (LLM, conf=0.94)
- Partly supportedcites [115] sourceExperimental — accuracy not yet measured
The Results sections on ANGPTL3 inactivation and ANGPTL8’s effects report that GPIHBP1-bound LPL is substantially protected from ANGPTL3 inhibition. They describe heparin as a means of releasing LPL for measurement after treatment, not as protecting it from inhibition. No page numbers are available in our copy. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“ANGPTL3-ANGPTL8 double knockout mice have higher body temperatures and appear to be more sensitive to sympathetic stimulation than wild-type mice (21).”
What the sources say
- Supportedcites [21] source
The Results section reports higher rectal temperatures in fed ANGPTL3/8 double-knockout mice than in wild-type mice at ambient temperature. The Discussion reports a greater thermogenic response to a β3-adrenergic agonist and infers increased sensitivity to adrenergic stimulation. The temperature difference was not observed at thermoneutrality. (LLM, conf=0.91)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Several studies have identified the N-terminal cleavage product to be necessary and sufficient for lipase inhibition (107, 123, 124).”
What the sources say
- Partly supportedcites [107] sourceExperimental — accuracy not yet measured
The Results section (page unavailable) reports that the N-terminal fragment inhibits lipolysis by LPL, supporting sufficiency. It also says full-length ANGPTL3 inhibits LPL equally well in vitro, so the fragment is not shown to be necessary for lipase inhibition. The Discussion treats cleavage as important for activation in vivo, not as an established requirement for inhibition in all conditions. (LLM, conf=0.90)
- Partly supportedcites [123] sourceExperimental — accuracy not yet measured
The “ANGPTL3 Inhibited EL Activity In Vitro” section reports that a recombinant N-terminal ANGPTL3 region suppressed endothelial lipase activity similarly to full-length ANGPTL3, supporting its sufficiency in that assay. It does not establish that the naturally cleaved N-terminal product is necessary for lipase inhibition; the loss-of-inhibition experiment instead mutated a putative heparin-binding site within the N-terminal region. No page number is provided in our copy. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [124] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“All three studies also found that ANGPTL8 is expressed primarily in the adipose tissue and liver of mice and that expression was much higher in the fed state than in the fasted state.”
What the sources say
- Supportedcites [19] source
The section “ANGPTL8 Expression Is Regulated by Food Intake in an SREBP-1c-Independent Manner” reports that mouse ANGPTL8 mRNA is most abundant in liver, with lower levels in adipose tissue, and that fasting markedly reduces expression while refeeding restores it (Fig. 5A). It also notes substantial expression in the adrenals, a nuance the citing sentence omits. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [35] source
- Not checked — no full text of the sourcecites [139] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In contrast, Mysling et al. (52) found that, like ANGPTL4, ANGPTL3 could inhibit LPL by unfolding or sterically changing the active domain of LPL, though its potency was far less than that of ANGPTL4.”
What the sources say
- Supportedcites [52] source
The Results section, “Unfolding catalyzed by intact ANGPTL3,” reports that ANGPTL3 accelerates unfolding of an LPL catalytic-domain peptide, inactivating LPL, but is less effective than equimolar ANGPTL4. This supports the claim’s proposed unfolding mechanism and potency comparison. (LLM, conf=0.94)
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“They also determined that ANGPTL3 inhibition of LPL was reversible and that heparin protected LPL from inhibition (55).”
What the sources say
- Supportedcites [55] source
The Discussion states that ANGPTL3 mainly causes reversible inhibition of LPL catalytic activity and that heparin protected LPL from ANGPTL3 at relatively low concentrations. The Abstract also reports that heparin overcame ANGPTL3’s inhibitory effect in the biochemical assay. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“They found that ANGPTL3 reduced the catalytic activity of LPL, but did not increase the rate of self-inactivation.”
What the sources say
- Partly supportedcites [55] sourceExperimental — accuracy not yet measured
The Results report that ANGPTL3 inhibited LPL’s initial catalytic activity. They also say it did not *significantly* accelerate inactivation beyond LPL’s self-inactivation, while noting a limited ability to accelerate inactivation; the categorical claim that it did not increase the rate omits that qualification. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“As with ANGPTL4, ANGPTL3 oligomerizes, appearing to form trimers or hexamers, and oligomerization is mediated by the N-terminal domain (72, 100).”
What the sources say
- Partly supportedcites [72] sourceExperimental — accuracy not yet measured
The section on higher-order structures and Fig. 3C report that ANGPTL3 forms oligomeric complexes, supporting the oligomerization claim. The copy does not identify those complexes as trimers or hexamers, or establish that ANGPTL3 oligomerization is mediated by its N-terminal domain; its N-terminal disulfide-bond discussion concerns ANGPTL4. Page numbers are not available in the supplied copy. (LLM, conf=0.88)
- Partly supportedcites [100] sourceExperimental — accuracy not yet measured
The Results (page unavailable) show that N-terminal ANGPTL3 constructs form trimers and hexamers. The Discussion (page unavailable) cautions that only N-terminal constructs were tested and that full-length ANGPTL3 may have a different oligomeric state. The findings show that the N-terminal domain can oligomerize, but do not establish that it mediates oligomerization of the full-length protein. (LLM, conf=0.84)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Chronic overfeeding and obesity can lead to shifts in fat partitioning, ectopic lipid deposition, and metabolic disease (155–157).”
What the sources say
- Supportedcites [155] source
The Introduction describes chronic excess intake and explains that, as adipose tissue becomes less effective at storing fat in common obesity, excess lipid may reach other tissues. It links this proposed shift in fat partitioning and ectopic accumulation to insulin resistance and other metabolic diseases. The claim’s ‘can lead to’ wording reflects that qualification; the paper’s own feeding experiment was acute and conducted in lipodystrophic mice. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [156] source
- Partly supportedcites [157] sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) links diet-induced obesity with increased circulating lipids, altered tissue lipid metabolism, insulin resistance, and cardiovascular complications. Summary, Part 2 (page unavailable) reports cardiac lipid accumulation and dysfunction with diet-induced obesity and nutrient overload. These passages support ectopic lipid deposition and related disease in the heart, but do not establish the broader shift in body-wide fat partitioning described in the claim. (LLM, conf=0.78)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“As discussed below, more recent studies have shown that ANGPTL3 forms of complex with ANGPTL8 and that this complex is most likely the physiologically relevant LPL inhibitor (19, 54, 115, 137, 138).”
What the sources say
- Partly supportedcites [19] sourceExperimental — accuracy not yet measured
The Discussion reports that ANGPTL3 and ANGPTL8 physically interact and coimmunoprecipitate, supporting the complex portion of the claim. It does not establish that their complex is the physiologically relevant LPL inhibitor: the Discussion treats a functional complex as one possible mechanism, and the A B section reports no significant decrease in plasma lipolytic activity after ANGPTL8 overexpression. (LLM, conf=0.87)
- Supportedcites [54] source
The Results section reports that ANGPTL3 and ANGPTL8 form a complex that inhibits LPL 186-fold more potently than ANGPTL3 alone. The Discussion proposes that circulating ANGPTL3/8 inhibits LPL in skeletal muscle after feeding, supporting the claim’s hedged description of its physiological relevance; the paper does not present it as the sole LPL inhibitor in every condition. Page numbers were not available in our copy. (LLM, conf=0.88)
- Supportedcites [115] source
The Abstract (Results and Conclusions) reports that ANGPTL3–ANGPTL8 forms a complex that inhibits LPL far more effectively than either protein alone; the individual proteins inhibited LPL only at concentrations far above physiological levels. The Discussion says the complex is necessary for efficient LPL inhibition and finds no evidence that ANGPTL3 alone reaches inhibitory concentrations physiologically. (LLM, conf=0.92)
- Partly supportedcites [137] sourceExperimental — accuracy not yet measured
The Abstract and Results show that ANGPTL3 and ANGPTL8 form an inhibitory complex: ANGPTL8 inhibits LPL in the presence of ANGPTL3, and coexpression raises triglycerides in mice more than ANGPTL3 alone. The paper does not establish that the complex is the predominant physiologically relevant LPL inhibitor; it also reports that ANGPTL3 inhibits LPL independently of ANGPTL8. Page numbers are unavailable in our copy. (LLM, conf=0.82)
- Partly supportedcites [138] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports ANGPTL3–ANGPTL8 complex formation and proposes that the complex inactivates LPL in the fed state. But it also says ANGPTL3 can inhibit LPL on its own at concentrations found in human plasma. The paper therefore supports a physiological role for the complex, not the stronger implication that it is the physiologically relevant inhibitor rather than ANGPTL3 alone. (LLM, conf=0.84)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Unfortunately, targeting ANGPTL4 with an anti-ANGPTL4 antibody in mice fed a high-fat diet led to intestinal abnormalities, chylous ascites, lymph node inflammation, and premature death (29)”
What the sources say
- Partly supportedcites [29] sourceExperimental — accuracy not yet measured
The Results report chylous ascites, mesenteric lymph-node pathology, and rare, mild intestinal lesions in high-fat-diet-fed mice treated with anti-ANGPTL4 antibody. The reduced survival described in the Results and Discussion concerns ANGPTL4 knockout mice, not antibody-treated mice; the antibody finding does not support the claim of premature death. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Like mice, humans deficient in ANGPTL3, ANGPTL4, or ANGPTL8 have lower plasma triglycerides (56–58, 163–166).”
What the sources say
- Partly supportedcites [56] sourceExperimental — accuracy not yet measured
The Results section reports lower triglyceride levels in human carriers of inactivating ANGPTL4 variants. The Discussion refers to triglyceride-lowering ANGPTL8 mutations, but does not establish that they cause ANGPTL8 deficiency; the passages do not report lower triglycerides in humans deficient in ANGPTL3. (LLM, conf=0.88)
- Partly supportedcites [57] sourceExperimental — accuracy not yet measured
The ANGPTL4 loss-of-function results section reports that carriers had triglyceride levels averaging 35% lower than noncarriers. The cited paper does not provide corresponding evidence for ANGPTL3 or ANGPTL8, so it supports only the ANGPTL4 part of the sentence. (LLM, conf=0.88)
- Partly supportedcites [58] sourceExperimental — accuracy not yet measured
The Abstract reports lower plasma triglycerides in human carriers of ANGPTL4 variants, including E40K, and says several variants found in the low-triglyceride group are predicted to truncate the protein or disrupt splicing. This supports the ANGPTL4 portion of the multi-citation sentence, but the paper does not establish that those humans were deficient in ANGPTL4; it does not provide human findings for ANGPTL3 or ANGPTL8. (LLM, conf=0.83)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In the case of ANGPTL3, loss of ANGPTL3 results not only in hypotriglyceridemia, but in familial combined hypolipidemia (108, 109, 116–118).”
What the sources say
- Supportedcites [108] source
The Results report a 62% reduction in triglycerides among carriers of two mutated ANGPTL3 alleles. The Discussion concludes that complete ANGPTL3 deficiency in homozygous carriers produces the full familial combined hypolipidemia phenotype; partial deficiency does not. (LLM, conf=0.91)
- Supportedcites [109] source
The Discussion reports low triglyceride levels in carriers of ANGPTL3 nonsense mutations and identifies familial combined hypolipidemia in people with two nonsense alleles. This supports the claim, with the qualification that the full combined phenotype was observed in people with both defective alleles. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [116] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Chadwick et al. (20) used CRISPR-mediated base editing to induce ANGPTL3 deficiency in 5-wk-old mice and found that this gene editing reduced ANGPTL3 expression, plasma triglycerides, and total cholesterol levels in both normal and hyperlipidemic mice.”
What the sources say
- Partly supportedcites [20] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“For example, targeting ANGPTL4 could potentially increase adiposity and increase glucose tolerance, as it does in mice (31–33, 84)”
What the sources say
- Partly supportedcites [31] sourceExperimental — accuracy not yet measured
The Results section reports improved glucose tolerance in mice lacking ANGPTL4 in adipose tissue. But the Discussion reports no change in fat mass or adipocyte size despite increased fatty-acid uptake, so this paper does not support the claim that targeting ANGPTL4 increases adiposity. Page numbers were not available in our copy. (LLM, conf=0.90)
- Partly supportedcites [32] sourceExperimental — accuracy not yet measured
The Results report improved glucose tolerance in adipocyte-specific ANGPTL4 knockout mice after 12 weeks of high-fat feeding, and greater fat mass after six months. The Discussion says the glucose-tolerance improvement mostly disappeared with longer feeding. Thus, the paper supports both potential effects in mice, but not their persistence together at the time increased adiposity was observed. (LLM, conf=0.86)
- Partly supportedcites [33] sourceExperimental — accuracy not yet measured
The Discussion reports improved glucose and insulin tolerance in mice lacking ANGPTL4 in brown adipose tissue. But the Results section on high-fat-diet feeding reports no difference in fat mass or body weight between those mice and controls, so this paper does not support the claimed increase in adiposity. (LLM, conf=0.90)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
In the paper
“The resulting decrease in ANGPTL4 protein leads to increased LPL activity in BAT, increasing uptake of triglycerides for thermogenic oxidation (71).”
What the sources say
- Not checked yetcites [71] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“They showed that injection of ANGPTL4 could increase plasma triglycerides and that recombinant ANGPTL4 could inhibit LPL in vitro (48).”
What the sources say
- Not checked — no full text of the sourcecites [48] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Dijk et al. (71) also observed that neither whole body knockout of ANGPTL4 nor ANGPTL4 overexpression had a significant effect on body temperature after prolonged cold exposure.”
What the sources say
- Not checked yetcites [71] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These increases require LPL activity, suggesting a shift in LPL regulation (68).”
What the sources say
- Not checked — no full text of the sourcecites [68] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here, we examine three such extracellular inhibitors, ANGPTL4, ANGPTL3, and ANGPTL8, which have emerged as key regulators of LPL, acting in specific tissues and at specific times to modulate LPL activity and adjust lipid partitioning.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition to their role in regulating plasma triglyceride levels, ANGPTL3, ANGPTL4, and ANGPTL8 have been associated with numerous physiological roles including stem-cell renewal, angiogenesis, and inflammation (42–45).”
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, under fasting conditions, ANGPTL4 would inhibit LPL and reduce triglyceride delivery to adipose tissues.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, they reported that transgenic overexpression of ANGPTL4 increased plasma triglycerides and reduced LPL activity measured in postheparin plasma.”
What the sources say
- Not checked — no full text of the sourcecites [16] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Angptl4 is highly expressed in adipose tissue (46, 47) and expression in adipose is quickly induced by fasting (16, 46, 62, 63).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Treating these cells with either recombinant ANGPTL4 or with LPL inhibitors greatly reduces both lipid uptake and cytokine release, suggesting that ANGPTL4 protects from lipid-induced inflammatory responses (59).”
What the sources say
- Not checked yetcites [59] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Unlike angiopoietin proteins, ANGPTL proteins do not bind the receptor tyrosine kinase Tie2, but may still contribute to angiogenesis (12, 14).”
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Singh et al. (33) found that mice lacking ANGPTL4 specifically in BAT did have slightly higher body temperatures after acute cold exposure, but did not test the effects of prolonged exposure.”
What the sources say
- Not checked yetcites [33] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Each of the ANGPTL proteins contain a signal peptide and can be secreted from cells.”
What the sources say
- Not checked yetcites [13] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In humans, ANGPTL5 is expressed in several tissues, including high expression in adipose tissue (40).”
What the sources say
- Not checked yetcites [40] source
Checked before — its earlier verdict is held back until a new check runs.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not checked yet
In the paper
“Ectopic deposition of fat to tissues such as liver and skeletal muscle can drive metabolic dysfunction and lead to metabolic disease (reviewed in Ref. 3).”
What the sources say
- Not checked — no full text of the sourcecites [3] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Cold exposure did not increase LPL activity in white adipose tissue, nor was ANGPTL4 expression decreased (71), indicating that these changes were specific to brown adipose tissue.”
What the sources say
- Not checked yetcites [71] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“They also found that fasting induced liver expression of FIAF.”
What the sources say
- Not checked yetcites [46] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“LPL is secreted by the parenchymal cells of these tissues, i.e., the adipocytes, cardiomyocytes, and myocytes (6) and then transported across capillary endothelial cells by the endothelial cell protein glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) (7).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“LPL expression is high in macrophages and LPL activity can increase lipid uptake and foam cell formation when macrophages are exposed to triglyceride-rich lipoproteins (74).”
What the sources say
- Not checked yetcites [74] source
Checked before — its earlier verdict is held back until a new check runs.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“In adipose-specific ANGPTL4 knockout mice, LPL activity is increased in adipose tissue but not in other tissues (31, 32),”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Conversely, ANGPTL4-deficient mice had lower than normal plasma triglycerides and higher postheparin-plasma LPL activity (16).”
What the sources say
- Not checked — no full text of the sourcecites [16] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“LPL is expressed highly in tissues that consume or store fat, including heart, skeletal muscle, all adipose depots, and the mammary gland (2–5).”
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“In mice, LPL-deficiency leads to neonatal death due to the inability of pups to properly utilize the triglyceride-rich milk from their mothers (10).”
What the sources say
- Not checked yetcites [10] source
Checked before — its earlier verdict is held back until a new check runs.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“Single nucleotide polymorphisms (SNPs) in ANGPTL5 are associated with plasma triglyceride levels in humans (40).”
What the sources say
- Not checked yetcites [40] source
Checked before — its earlier verdict is held back until a new check runs.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not checked yet
In the paper
“Mice deficient in ANGPTL6 (also known as angiopoietin-related growth factor) become obese, insulin resistant, and accumulate lipid in skeletal muscle and liver (41).”
What the sources say
- Not checked — no full text of the sourcecites [41] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The physiological data would therefore suggest that circulating ANGPTL3 encounters and interacts with LPL in the vasculature, inhibiting its lipase activity and reducing clearance of TG-rich lipoprotein particles.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For many years, LPL was thought to be active only as a homodimer, and initial studies suggested that ANGPTL4 inactivated LPL by converting active dimers to inactive monomers (49).”
What the sources say
- Not checked yetcites [49] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“When cleaved, the C-terminal domain dissociates to monomers, but the N-terminal region can remain oligomerized (89, 96).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“LPL is known to facilitate the uptake of lipoproteins in the liver (127–130).”
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“found a 460-amino acid protein with the conserved secondary structure of the ANGPTL family (a signal peptide followed by an N-terminal coil-coil domain with a linker leading to a C-terminal fibrinogen-like domain).”
What the sources say
- Not checked — no full text of the sourcecites [103] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Shimamura et al. (123), who found that ANGPTL3 inhibited EL in a dose-dependent manner and that reexpression of ANGPTL3 in ANGPTL3-knockout mice increased plasma HDL-C levels.”
What the sources say
- Not checked yetcites [123] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Wang et al. (106) found that ANGPTL3 deficiency did increase TG-derived fatty acid uptake into heart and skeletal muscle, but that ANGPTL3 deficiency simultaneously decreased uptake into white adipose tissue.”
What the sources say
- Not checked yetcites [106] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In some studies, germ-free mice were protected from weight gain, and ANGPTL4 appeared to be necessary for this protection (30, 82).”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, in other studies, germ-free mice were not protected from weight gain (83).”
What the sources say
- Not checked yetcites [83] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Curiously, although ANGPTL3 expression is regulated by LXR, insulin, leptin, and thyroid hormone (111–114),”
What the sources say
- Not checked yetcites [111] source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked — no full text of the sourcecites [112] source
- Not checked — no full text of the sourcecites [113] source
- Not checked yetcites [114] source
Checked before — its earlier verdict is held back until a new check runs.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“ANGPTL3 is expressed in and secreted from the liver and circulates in the bloodstream (15, 40, 72, 103).”
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“microRNA-134m, which suppresses ANGPTL4 expression in macrophages, increases foam cell formation in an LPL-dependent manner (75, 76).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In mice, overexpression of ANGPTL4 reduces triglyceride uptake into the heart and protects against oxidative stress after either oral fat loading or high-fat diet feeding (27, 79).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the absence of ANGPTL3, LPL would remain active and clearance of VLDL and chylomicrons would increase.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The induction of ANGPTL8 expression results in the formation of ANGPTL4-ANGPTL8 complexes, which greatly reduce the ability of ANGPTL4 to inhibit LPL.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“ANGPTL3 contains a protease cleavage site, and in vivo can be cleaved into two domains both intracellularly by PCSK3 and extracellularly by PACE4 (107, 124, 131, 132).”
What the sources say
- Not checked yetcites [107] source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked — no full text of the sourcecites [124] source
- Not checked yetcites [131] source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked yetcites [132] source
Checked before — its earlier verdict is held back until a new check runs.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not checked yet
In the paper
“Chen et al. (154) showed that ANGPTL4-ANGPTL8 complexes may actually stimulate LPL activity at 22°C.”
What the sources say
- Not checked — no full text of the sourcecites [154] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Two independent studies found that when high-fat diet was fed to mice without adipose ANGPTL4, these mice had increased adipose triglyceride deposition and improved glucose tolerance compared with wild-type mice (31, 32).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Liu et al. (132) found that ANGPTL3 increased the cleavage of LPL by PACE4, but not PCKS5.”
What the sources say
- Not checked yetcites [132] source
Checked before — its earlier verdict is held back until a new check runs.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not checked yet
In the paper
“Using such a diet, Janssen et al. (84) found that ANGPTL4-deficient mice gained more weight but were more glucose tolerant than wild-type mice.”
What the sources say
- Not checked yetcites [84] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Chen et al. (152) recently reported that ApoA5 binds ANGPTL3-ANGPTL8 complexes, but not ANGPTL3, ANGPTL4, or ANGPTL8 alone, and greatly reduces the ability of this complex to inhibit LPL.”
What the sources say
- Not checked yetcites [152] source
Checked before — its earlier verdict is held back until a new check runs.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“The N-terminal domain contains the conserved SE1/LPL inhibitory domain (amino acids 32–55), a domain found in ANGPTL3 and ANGPTL4 known to be important for the binding and inhibition of LPL (17).”
What the sources say
- Not checked yetcites [17] source
Checked before — its earlier verdict is held back until a new check runs.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not checked yet
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, ANGPTL4-ANGPTL8 complexes, which retain the ability to bind LPL, appear to protect LPL from inhibition by the much more potent ANGPTL3-ANGPTL8 complexes.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Haller et al. (137) found that this domain was incapable of inhibiting LPL when ANGPTL8 was alone, but was necessary for LPL inhibition by ANGPTL3-ANGPTL8 complexes.”
What the sources say
- Not checked yetcites [137] source
Checked before — its earlier verdict is held back until a new check runs.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not checked yet
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Circulating ANGPTL3-ANGPTL8 complexes inhibit LPL in oxidative tissues, such as heart and skeletal muscle, blunting triglyceride uptake into these tissues and thus allowing more uptake into adipose tissue.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“disruption of ANGPTL3 primarily effects triglyceride metabolism and lipid partitioning in the fed state despite the fact that ANGPTL3 expression itself is not feeding induced (72, 106).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“With prolonged cold exposure, expression of ANGPTL4 decreases in BAT and increases in WAT (33, 70, 71).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In initial studies, Evinacumab, a human anti-ANGPTL3 monoclonal antibody, lowered triglyceride levels by 76%, LDL-cholesterol by 23.2%, and HDL-cholesterol by 18.4% in healthy individuals (165).”
What the sources say
- Not checked yetcites [165] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In initial studies, treatment with Vupanorsen was associated with a 33%–63% decrease in triglycerides as well as reductions in Apo-C III, remnant and total cholesterol, HDL-C, and LDL-C (169).”
What the sources say
- Not checked — no full text of the sourcecites [169] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Lowering ANGPTL3, ANGPTL4, or ANGPTL8 would each be expected to lower plasma triglycerides, but as these proteins act at different times and at different places, systemic effects could vary substantially.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Triglyceride metabolism changes with age, but the mechanisms behind these changes are largely unknown (reviewed in Ref. 184).”
What the sources say
- Not checked yetcites [184] source
Checked before — its earlier verdict is held back until a new check runs.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“For example, GPIHBP1-deficient mice exhibit severe hypertriglyceridemia and have very little LPL-mediated triglyceride uptake (8).”
What the sources say
- Not checked yetcites [8] source
Checked before — its earlier verdict is held back until a new check runs.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not checked yet
In the paper
“One recent study suggested that ANGPTL3-ANGPTL8 complexes promote furin-mediated cleavage of LPL, but the levels of cleavage observed were not sufficient to explain the level of LPL inhibition (179).”
What the sources say
- Not checked — no full text of the sourcecites [179] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
Fatty acids liberated by LPL-mediated lipolysis are largely taken up by the tissue in which LPL is located.
“The fatty acids liberated by LPL-mediated lipolysis are largely taken up by the tissue in which LPL is located.”
The paper relies on this without support.
The tissue distribution of fatty acids shifts according to metabolic state and is important for maintaining metabolic homeostasis.
“The tissue distribution of fatty acids, often referred to as fatty acid partitioning, shifts according to metabolic state and is important for maintaining metabolic homeostasis.”
The paper relies on this without support.
The mouse models used in the cited studies are adequate models for human ANGPTL biology and lipid metabolism.
“Like mice, humans deficient in ANGPTL3, ANGPTL4, or ANGPTL8 have lower plasma triglycerides (56–58, 163–166).”
The paper relies on this without support.
The detrimental effects of ANGPTL4 inhibition observed in mice and monkeys predict similar risks in humans.
“Given the detrimental effects observed in mice and monkeys, targeting ANGPTL4 in humans certainly warrants caution, but it should be noted that thus far these detrimental effects have not been reported in humans with ANGPTL4 deficiency.”
The paper relies on this without support.
Endothelial lipase, pancreatic lipase, and hepatic lipase all contribute to plasma lipoprotein metabolism.
“As endothelial lipase, pancreatic lipase, and hepatic lipase all contribute to plasma lipoprotein metabolism”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Abstract
“This finding is consistent with the observation that overexpression of ANGPTL4 in mice impaired glucose intolerance (26).”
§ Abstract
“These studies suggested that with high-fat feeding, ANGPTL4 would normally direct triglycerides away from adipose, increasing ectopic lipid deposition and glucose intolerance.”
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
“10.1016/j.cell.2013.04.008”
Cited work 10.1016/j.cell.2013.04.008 · retracted 2017-01-01 · notice 10.1016/j.cell.2016.12.017 · this paper published 2021-10-01
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“10.5551/jat.40212”
Cited work 10.5551/jat.40212 · retracted 2021-10-05 · notice 10.5551/jat.rt40212 · this paper published 2021-10-01
Citations
Cites
2 retracted
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Self-citation
Research works printed but not linked: 1
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Cited by
Sorted by citations
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Metadata
- Authors
- Sylvers-Davie, K. L., & Davies, B. S. J.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Davies, Brandon S. J.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2021-10-01
- Volume
- 321
- Issue
- 4
- Pages
- E493-E508
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC8560382
- OpenAlex
- W3189264236
- Semantic Scholar
- 288a79590d70fa98a6536f7f6e35cd650ed25ab8
- Cited by
- 154
- References
- 186
- Citations by year
- 2026: 38 · 2025: 43 · 2024: 36 · 2023: 29 · 2022: 5 · 2021: 3
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Heart, Lung, and Blood Institute (R01HL130146, R01HL134787)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- ANGPTL3, ANGPTL4, ANGPTL8, angiopoietin-like proteins, lipoprotein lipase, triglyceride-rich lipoproteins, lipoprotein metabolism, triglyceride metabolism, fat partitioning, fatty acid uptake
- MeSH terms
- Angiopoietin-like Proteins, Angiopoietin-Like Protein 4, Angiopoietin-Like Protein 3, Angiopoietin-Like Protein 8, Humans, Lipoproteins, Triglycerides, Peptide Hormones, Lipid Metabolism
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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