Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8

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

• Supported

  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)

  cites [46] source
• Supported

  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)

  cites [47] source

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

• Supported

  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)

  cites [71] source

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 supported

  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)

  cites [13] sourceExperimental — accuracy not yet measured

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

• Supported

  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)

  cites [73] source

In the paper

“The family currently has eight known members, ANGPTL1-8, with pleiotropic functions (13).”

What the sources say

• Supported

  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)

  cites [13] source

In the paper

“GPIHBP1 also anchors LPL to the capillary wall during lipolysis of lipoproteins (8, 9).”

What the sources say

• Supported

  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)

  cites [8] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [9] source

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

• Supported

  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)

  cites [84] source

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 supported

  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)

  cites [49] sourceExperimental — accuracy not yet measured
• Supported

  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)

  cites [51] source
• Partly supported

  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)

  cites [72] sourceExperimental — accuracy not yet measured
• Partly supported

  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)

  cites [89] sourceExperimental — accuracy not yet measured
• Supported

  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)

  cites [90] source

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 supported

  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)

  cites [52] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [97] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [98] source

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
• Supported

  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)

  cites [18] source
• Supported

  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)

  cites [106] source

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

• Supported

  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)

  cites [105] source

In the paper

“LPL’s endothelial cell receptor GPIHBP1 protects LPL from ANGPTL3 inhibition as does heparin (60, 115).”

What the sources say

• Supported

  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)

  cites [60] source
• Partly supported

  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)

  cites [115] sourceExperimental — accuracy not yet measured

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 supported

  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)

  cites [107] sourceExperimental — accuracy not yet measured
• Partly supported

  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)

  cites [123] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [124] source

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

• Supported

  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)

  cites [19] source
• ?Not checked — no full text of the sourcecites [35] source
• ?Not checked — no full text of the sourcecites [139] source

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

• Supported

  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)

  cites [52] source

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 supported

  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)

  cites [55] sourceExperimental — accuracy not yet measured

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 supported

  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)

  cites [72] sourceExperimental — accuracy not yet measured
• Partly supported

  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)

  cites [100] sourceExperimental — accuracy not yet measured

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

• Supported

  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)

  cites [155] source
• ?Not checked — no full text of the sourcecites [156] source
• Partly supported

  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)

  cites [157] sourceExperimental — accuracy not yet measured

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 supported

  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)

  cites [19] sourceExperimental — accuracy not yet measured
• Supported

  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)

  cites [54] source
• Supported

  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)

  cites [115] source
• Partly supported

  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)

  cites [137] sourceExperimental — accuracy not yet measured
• Partly supported

  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)

  cites [138] sourceExperimental — accuracy not yet measured

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 supported

  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)

  cites [29] sourceExperimental — accuracy not yet measured

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 supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [20] sourceExperimental — accuracy not yet measured

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 supported

  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)

  cites [31] sourceExperimental — accuracy not yet measured
• Partly supported

  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)

  cites [32] sourceExperimental — accuracy not yet measured
• Partly supported

  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)

  cites [33] sourceExperimental — accuracy not yet measured

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

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

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

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

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.”

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

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [42] source
• ?Not checked — no full text of the sourcecites [43] source
• ?Not checked — no full text of the sourcecites [44] source
• ?Not checked — no full text of the sourcecites [45] source

In the paper

“Thus, under fasting conditions, ANGPTL4 would inhibit LPL and reduce triglyceride delivery to adipose tissues.”

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

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

• ?Not checked — no full text of the sourcecites [16] source
• Not checked yetcites [46] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [62] source
• Not checked yetcites [63] source

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

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

• ?Not checked — no full text of the sourcecites [12] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [14] source

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

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

In the paper

“In humans, ANGPTL5 is expressed in several tissues, including high expression in adipose tissue (40).”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [40] source

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

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

In the paper

“They also found that fasting induced liver expression of FIAF.”

What the sources say

• Not checked yetcites [46] source

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

• ?Not checked — no full text of the sourcecites [6] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [7] source

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 yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [74] source

In the paper

“In adipose-specific ANGPTL4 knockout mice, LPL activity is increased in adipose tissue but not in other tissues (31, 32),”

What the sources say

• Not checked yetcites [31] source
• Not checked yetcites [32] source

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

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

• ?Not checked — no full text of the sourcecites [2] source
• ?Not checked — no full text of the sourcecites [3] source
• ?Not checked — no full text of the sourcecites [4] source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [5]

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 yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [10] source

In the paper

“Single nucleotide polymorphisms (SNPs) in ANGPTL5 are associated with plasma triglyceride levels in humans (40).”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [40] source

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

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.”

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

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [53] source
• Not checked yetcites [100] source

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
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [120] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [121] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [122] source

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

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

• Not checked yetcites [89] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [96] source

In the paper

“LPL is known to facilitate the uptake of lipoproteins in the liver (127–130).”

What the sources say

• ?Not checked — no full text of the sourcecites [127] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [128] source
• ?Not checked — no full text of the sourcecites [129] source
• Not checked yetcites [130] source

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

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

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

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).”

What the sources say

• Not checked yetcites [30] source
• Not checked yetcites [82] source

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

In the paper

“Curiously, although ANGPTL3 expression is regulated by LXR, insulin, leptin, and thyroid hormone (111–114),”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [111] source
• ?Not checked — no full text of the sourcecites [112] source
• ?Not checked — no full text of the sourcecites [113] source
• Not checked yet

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  cites [114] source

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

• ?Not checked — no full text of the sourcecites [15] source
• Not checked yet

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  cites [40] source
• Not checked yetcites [72] source
• ?Not checked — no full text of the sourcecites [103] source

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

• ?Not checked — no full text of the sourcecites [75] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [76] source

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

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [86] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [87] source

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

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [27] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [79] source

In the paper

“In the absence of ANGPTL3, LPL would remain active and clearance of VLDL and chylomicrons would increase.”

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

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [21] source

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.”

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 yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [107] source
• ?Not checked — no full text of the sourcecites [124] source
• Not checked yet

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  cites [131] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [132] source

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

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

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [55] source

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

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [31] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [32] source

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 yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [132] source

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

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 yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [152] source

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 yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [17] source

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.”

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 yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [137] source

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.”

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

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [72] source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [106] source

In the paper

“With prolonged cold exposure, expression of ANGPTL4 decreases in BAT and increases in WAT (33, 70, 71).”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [33] source
• ?Not checked — no full text of the sourcecites [70] source
• Not checked yet

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  cites [71] source

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

In the paper

“Like mice, humans deficient in ANGPTL3, ANGPTL4, or ANGPTL8 have lower plasma triglycerides (56–58, 163–166).”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [56] source
• Not checked yetcites [57] source
• Not checked yet

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  cites [58] source

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

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [108] source
• Not checked yetcites [109] source
• ?Not checked — no full text of the sourcecites [116] source

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

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.”

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 yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [184] source

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 yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [8] source

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