The DOI matches its Crossref record; 153 of the 153 references it cites were found in a registry or an index; 15 of the 250 sources its claims cite were checked for support.
Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis
Open accessAbstract
Fibroblast growth factor 21 (FGF21) is an endocrine hormone derived from the liver that exerts pleiotropic effects on the body to maintain overall metabolic homeostasis. During the past decade, there has been an enormous effort made to understand the physiological roles of FGF21 in regulating metabolism and to identify the mechanism for its potent pharmacological effects to reverse diabetes and obesity. Through both human and rodent studies, it is now evident that FGF21 levels are dynamically regulated by nutrient sensing, and consequently FGF21 functions as a critical regulator of nutrient homeostasis. In addition, recent studies using new genetic and molecular tools have provided critical insight into the actions of this endocrine factor. This review examines the numerous functions of FGF21 and highlights the therapeutic potential of FGF21-targeted pathways for treating metabolic disease.
Overview
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Written from the paper’s full text.
TL;DR
This review synthesizes human and rodent evidence that fibroblast growth factor 21 (FGF21) is a liver-derived endocrine hormone that regulates nutrient homeostasis, macronutrient preference, thermogenesis, and stress responses, with potent pharmacological effects against obesity and diabetes. It highlights central nervous system actions as key to FGF21’s chronic metabolic benefits and discusses therapeutic promise alongside unresolved safety and mechanism questions.
Key findings
- FGF21 is dynamically regulated by nutritional state: fasting, low-protein diets, carbohydrate/fructose intake, ketogenic diets, and alcohol all alter circulating FGF21, while liver-derived FGF21 coordinates fasting/refeeding, protein restriction, and sweet-taste preference.
- Pharmacological FGF21 has strong metabolic effects: a single injection lowered plasma glucose by more than 50% in diabetic/obese animal models, and repeated administration increased metabolic rate and promoted weight loss; human trials with analogs LY2405319 and PF-05231023 reduced body weight and improved lipid profiles, though effects on glucose/insulin varied.
- The chronic metabolic effects of FGF21 on body weight and glucose homeostasis require CNS β-klotho, not adipose β-klotho; acute insulin sensitization instead requires direct FGF21 signaling to brown adipocytes.
- Human genetics link FGF21 variants to macronutrient intake and sweet preference: rs838133 and rs838145 associate with higher carbohydrate intake, and a UK Biobank analysis of 451,000 individuals found rs838133 associated with higher carbohydrate intake, body fat distribution, and blood pressure. Other reported numbers include an approximately eightfold increase in circulating FGF21 with excess carbohydrate, a half-life of approximately 0.4–2 hours, and human FGF21 cleavage between Pro-171 and Ser-172 by FAP.
Methods
- Narrative review of human and rodent studies, including genetic loss- and gain-of-function models, pharmacological FGF21 administration, clinical trials with FGF21 analogs, and human genetic association data.
- The paper synthesizes findings thematically across fasting/refeeding, ketogenic diets, protein restriction, macronutrient preference, alcohol, thermogenesis, cellular stress, CNS signaling, and translational trials; no primary experimental methods or systematic review protocol are reported.
Limitations
- The review states several unresolved controversies: whether FGF21 resistance exists in obesity, whether FGF21 is required for ketogenic-diet effects, whether FGF21 directly affects bone loss or female fertility, and whether extrahepatic FGF21 production has physiological relevance.
- It notes that mechanisms for adverse effects, including gastrointestinal issues, blood pressure changes, and the CNS–adipose circuit, remain unclear and require further study.
- Evident from the text: this is a narrative review without a stated systematic search strategy, inclusion criteria, or quantitative synthesis, and many conclusions rely on rodent models with acknowledged species differences in FGF21 biology and thermogenesis.
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Claims the paper makes
138 Not checked yet · 24 Own interpretation · 5 Supported · 4 Own result · 2 Partly supported · 2 No basis given · 1 Supported so far · 1 Mixed support · accuracy not yet measured
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“In addition, in humans, plasma FGF21 levels have been shown to be induced by increases in both glucose and insulin levels (31, 84, 110, 133), supporting a role during refeeding.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Physiological Role of FGF21 During Fasting and Refeeding
What the sources say
- Partly supportedcites [31] sourceExperimental — accuracy not yet measured
The Results (page unavailable) report that FGF21 rose modestly and with a delay after glucose ingestion, supporting a glucose-associated increase. They also report a correlation between the FGF21 response to fructose and the insulin response to a separate glucose challenge, but do not show that an increase in insulin induces FGF21. (LLM, conf=0.86)
- Partly supportedcites [84] sourceExperimental — accuracy not yet measured
The Results and discussion section (‘Dietary carbohydrate but not caloric excess increases circulating FGF21’; page unavailable) reports that carbohydrate overfeeding markedly increased plasma FGF21 in healthy men. The section on lipid and glucose homeostasis reports a small concurrent rise in insulin, but does not establish that increases in plasma glucose or insulin induced FGF21. (LLM, conf=0.86)
- Disputedcites [110] sourceExperimental — accuracy not yet measured
The Discussion (page not supplied) says that insulin, rather than glucose per se, regulates FGF21 secretion in adult humans. The paper supports an insulin-induced rise but contradicts the claim that increased glucose itself induces the rise. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
- Partly supportedcites [133] sourceExperimental — accuracy not yet measured
The Results and Discussion section reports that plasma FGF21 in healthy humans rose three-fold after 24 hours of dextrose-induced hyperglycemia, supporting the glucose portion of the claim. It does not report that increased insulin levels induced plasma FGF21 in humans, so that portion is unsupported. No page number is available in our copy. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Thus, to explore the significance of FGF21 signaling directly to adipose tissues, investigators crossed mice with a conditional Klb allele with Adiponectin-Cre transgenic mice (11), which drive Cre expression specifically in adipose tissues (75).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 Signals to Adipose Tissues to Acutely Increase Insulin Sensitivity
What the sources say
- Supportedcites [11] source
The Results section states that Adiponectin-Cre mice drive Cre expression in both white and brown adipocytes. It also reports that crossing these mice with KLBfl/fl mice ablated β-klotho specifically in adipose tissue depots. Page numbers are not provided in our copy. (LLM, conf=0.93)
- Supportedcites [75] source
The Results report that Cre mRNA in Adipoq-Cre mice was found exclusively in the fat pads, with no detectable expression in heart, muscle, or liver. The Discussion also identifies Adipoq-Cre as the most specific of the three tested lines for white and brown fat. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“Although FGF21 signals directly to adipose tissues to acutely enhance insulin sensitivity, the chronic effects of FGF21 on body weight and improved insulin sensitivity are retained in adipose-specific Klb knockout mice (Klbfl/fl;Adiponectin-Cre) (11, 74), demonstrating that direct signaling to adipose tissues is not required for the chronic effects of FGF21 (Figure 4).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 and the Central Nervous System
What the sources say
- Supportedcites [11] source
The Results section identifies KLB AdipoKO mice as Klbfl/fl mice crossed with Adiponectin-Cre mice. It reports that extended FGF21 treatment lowered body weight and improved insulin sensitivity in these mice, with metabolic improvements similar to those in treated controls. The finding is specifically for diet-induced obese mice receiving extended pharmacological FGF21 treatment. (LLM, conf=0.94)
- Partly supportedcites [74] sourceExperimental — accuracy not yet measured
The Results section on adipose β-Klotho (page unavailable) reports that two weeks of FGF21 reduced body weight and plasma glucose and insulin in both control and adiponectin-Cre Klb knockout mice. It does not establish that chronic FGF21 improved insulin sensitivity in the knockout mice: the insulin-sensitivity clamp results concern acute treatment, and the Discussion notes that the longer-term glycemic effects may be secondary to weight loss. (LLM, conf=0.86)
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“FGF21 levels can also be regulated by adipose-derived exosomes.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > Mechanisms Regulating FGF21 Activity
What the sources say
- Supportedcites [129] source
The section “FGF-21 as a Potential Target of Regulation by Circulating Exosomal miRNAs” reports that injected WT exosomes reduced hepatic FGF21 mRNA and circulating FGF21 in ADicerKO mice. It also reports reduced circulating FGF21 after injection of exosomes reconstituted with miR-99b. These mouse experiments support the claim that adipose-derived exosomes can regulate FGF21 levels. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Liver-specific, but not adipose-specific, Fgf21 knockout mice are susceptible to acute cold exposure (lasting 1–3 days) (M. Ameka, K.M. Markan & M.J. Potthoff, unpublished data).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21 and Adaptive Thermogenesis
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma FGF21 levels are induced acutely from the liver in response to cold exposure and liver-derived FGF21 signals to the CNS to increase sympathetic nerve activity to BAT and regulate core body temperature (Figure 3b) (M. Ameka, K.M. Markan & M.J. Potthoff, unpublished data).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21 and Adaptive Thermogenesis
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The expression levels and metabolic functions of FGF21 are dynamically impacted by nutritional status (37, 102).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > INTRODUCTION TO FGF21
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“FGF21 functions in target tissues that express the traditional FGF receptor FGFR1c and the obligate coreceptor β-klotho (2, 27, 71, 99, 124, 140).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > INTRODUCTION TO FGF21
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“FGF21 levels are dynamically regulated by nutrient sensing”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > Abstract
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In the paper
“Notably, despite the expression of Fgf21 mRNA in these tissues, under most physiological conditions, circulating levels of FGF21 are derived primarily from the liver (46, 86).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > INTRODUCTION TO FGF21
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- It may state two separate claims as one. 64
- Probably not a substantial claim. 4
- The quote only partly states this claim. 1
Every source the paper cites for this claim was checked and supports it.
In the paper
“Knockdown of hepatic Fgf21 using adenovirus-mediated expression of short hairpin RNAs directed against Fgf21 mRNA resulted in significantly elevated hepatic triglyceride and plasma lipid levels, and impaired ketosis (7).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21-Mediated Lipid Metabolism on a Ketogenic Diet
What the sources say
- Supportedcites [7] source
The Results report that adenovirus-mediated shRNA knockdown of FGF21 in mice on a ketogenic diet increased hepatic triglycerides and circulating lipids. They also report a significant, though relatively modest, reduction in serum ketones. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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 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
“The Fgf21 promoter has multiple ATF4 binding sites, and GCN2-mediated activation of ATF4 leads to the induction of hepatic and circulating levels of FGF21 (24, 68, 72).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21 Signals Protein Restriction
What the sources say
- Not checked yetcites [24] source
- Not checked yetcites [68] source
- Supportedcites [72] source
The Experimental Procedures identify distal and proximal ATF4 binding sites in the mouse FGF21 promoter. The Discussion links GCN2-dependent ATF4 activation to the acute induction of hepatic Fgf21 and circulating FGF21 during dietary protein restriction. It also notes that GCN2 is not required for the longer-term increase, so the claim should not be read as saying this pathway is always necessary. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Mice that lack FGF21 develop marked liver steatosis and injury in response to chronic alcohol consumption despite being able to clear ethanol as effectively as wild-type controls (26).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Alcohol, FGF21, and Liver Function
What the sources say
- Supportedcites [26] source
The Results section on chronic ethanol consumption in drinking water reports steatosis and liver injury in FGF21-KO mice compared with wild-type mice (Figure 6). The Discussion states that, in this 16-week drinking-water and chow model, the groups had the same serum ethanol levels and capacity to metabolize ethanol. The clearance finding is specific to this model; the paper reports impaired ethanol metabolism in a separate high-fat-diet model. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
“Fgf21 knockout mice exhibit increased hepatic lipogenesis and decreased β-oxidation following alcohol exposure (83).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Alcohol, FGF21, and Liver Function
What the sources say
- Supportedcites [83] source
In the Results section on hepatic lipogenesis, alcohol-fed FGF21 knockout mice had greater increases in lipogenic gene expression than wild-type mice. The Results section on fatty acid β-oxidation reports larger decreases in oxidation-related gene expression in the knockout mice. No page numbers are available in our copy. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Neither the inducible expression of a constitutively active FGFR1 protein specifically in adipose tissue (11) nor antibody-mediated activation of a chimeric human FGFR1 receptor in brown adipocytes (17) is sufficient to increase energy expenditure or affect body weight in vivo.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 and the Central Nervous System
What the sources say
- Partly supportedcites [11] 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.
- Partly supportedcites [17] 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.
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.
- Partly supported
A result the paper reports from its own data — 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 contrast to the studies supporting a role for adipose-derived FGF21 in regulating thermogenesis, recent work from our lab has found that liver-derived, but not adipose-derived, FGF21 regulates core body temperature during cold exposure.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21 and Adaptive Thermogenesis
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 result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma FGF21 levels are induced acutely from the liver in response to cold exposure and liver-derived FGF21 signals to the CNS to increase sympathetic nerve activity to BAT and regulate core body temperature (Figure 3b) (M. Ameka, K.M. Markan & M.J. Potthoff, unpublished data).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21 and Adaptive Thermogenesis
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
“Fibroblast growth factor 21 (FGF21) is an endocrine hormone derived from the liver that exerts pleiotropic effects on the body to maintain overall metabolic homeostasis.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > Abstract
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
“Unlike traditional FGFs, however, the FGF19 subfamily of FGFs, consisting of FGF19, FGF21, and FGF23, has reduced affinity for HSGAGs and diffuses into circulation to act on distal tissues (9, 106). Thus, these FGFs function as endocrine hormones.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > INTRODUCTION TO FGF21
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A myriad of studies ensued demonstrating that administering FGF21 to obese or diabetic rodents and primates markedly reduced body weight and significantly improved carbohydrate and lipid homeostasis (21, 64, 65, 141).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > INTRODUCTION TO FGF21
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, these conclusions have been controversial because other groups have reported that FGF21 is not required for regulating glucose homeostasis and ketosis induced by ketogenic diets (97, 123).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21-Mediated Lipid Metabolism on a Ketogenic Diet
plain- Asserted: passes — The authors put it forward as true.
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- 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.
In the paper
“However, when nutrients become available following a prolonged fast, FGF21 functions as a metabolic switch to facilitate the transition to the refed state by enhancing insulin-stimulated glucose uptake while acutely maintaining the actions of the fasting response (86).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Physiological Role of FGF21 During Fasting and Refeeding
What the sources say
- Not checked yetcites [86] source
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
“The overexpression of FGF21 was sufficient to increase hepatic gluconeogenesis, β-oxidation, and ketogenesis, whereas the loss of FGF21 prevented fasting-induced hepatic gluconeogenesis, β-oxidation, and ketogenesis in mice (105).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Physiological Role of FGF21 During Fasting and Refeeding
What the sources say
- Not checked yetcites [105] source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Low-protein diets (73, 85), amino acid starvation (25, 121), and the amino acid–depleting drug asparaginase (138) also induce plasma FGF21 levels.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21 Signals Protein Restriction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Consistent with these data, Fgf21 total knockout mice fed a ketogenic diet developed hepatosteatosis and exhibited impaired ketogenesis and glucose control (6).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21-Mediated Lipid Metabolism on a Ketogenic Diet
What the sources say
- Not checked yetcites [6] 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
“FGF21 is markedly induced in response to protein restriction (25, 73, 85) but not caloric restriction (73, 148).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21 Signals Protein Restriction
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
“FGF21 is markedly induced by ketogenic diets in rodents and has been proposed to be a key mediator of hepatic lipid metabolism during ketotic states (6, 7).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21-Mediated Lipid Metabolism on a Ketogenic Diet
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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“While FGFR1c is ubiquitously expressed, β-klotho expression is limited to metabolic tissues and confers specificity for FGF21 signaling.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > INTRODUCTION TO FGF21
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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 circulating levels of FGF21 are derived from the liver, as the genetic loss of Fgf21 specifically from the liver ablates plasma FGF21 levels during fasting (86).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Physiological Role of FGF21 During Fasting and Refeeding
What the sources say
- Not checked yetcites [86] 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
“Administration of FGF21 to the PVN of the hypothalamus restored corticosterone production and reversed the impaired hepatic gluconeogenesis observed in Fgf21 knockout mice (81).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Physiological Role of FGF21 During Fasting and Refeeding
What the sources say
- Not checked yetcites [81] 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
“Ad libitum feeding of sucrose for 6–24 hours gradually increases hepatic and plasma FGF21 levels in wild-type mice, and this effect is lost in liver-specific Fgf21 knockout mice (133).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Regulation of Macronutrient Intake and Sweet Taste Preference by FGF21
What the sources say
- Not checked yetcites [133] 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
“While fructose markedly and acutely increased plasma FGF21 levels in humans, glucose caused a delayed and gradual increase in plasma FGF21 levels (31).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Regulation of Macronutrient Intake and Sweet Taste Preference by FGF21
What the sources say
- Not checked yetcites [31] 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
“Consistent with these data in humans, Fgf21 total knockout mice exhibit an increased preference for simple sugars, but not lipids or protein (133).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Regulation of Macronutrient Intake and Sweet Taste Preference by FGF21
What the sources say
- Not checked yetcites [133] 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
“Specifically, these studies reported that variants rs838133 and rs838145 were associated with higher carbohydrate intake and that FGF21 was a candidate gene in the region (20, 127).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Regulation of Macronutrient Intake and Sweet Taste Preference by FGF21
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Finally, as would be predicted from the human SNP data, Klbfl/fl;CamK2a-Cre mice consume more alcohol and prefer alcohol more than wild-type control mice (116).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Alcohol, FGF21, and Liver Function
What the sources say
- Not checked yetcites [116] source
hedgedcorrelational- 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 rodents, pharmacological levels of FGF21 increase energy expenditure (64, 141), which results in increased food intake (54, 64).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Alcohol, FGF21, and Liver Function
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
“Interestingly, administering recombinant FGF21 (116) or the overexpression of FGF21 (125) significantly reduced alcohol preference but not plasma ethanol concentrations.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Alcohol, FGF21, and Liver Function
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
“Indeed, the administration of recombinant FGF21 to mice markedly reduces carbohydrate preference without affecting the preferences for lipid and protein (133).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Regulation of Macronutrient Intake and Sweet Taste Preference by FGF21
What the sources say
- Not checked yetcites [133] source
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
“Although variants around the FGF21 locus are associated with changes in macronutrient intake, they are not associated with obesity or type 2 diabetes (120).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Regulation of Macronutrient Intake and Sweet Taste Preference by FGF21
What the sources say
- Not checked yetcites [120] 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.
None of the sources cited for this claim have been checked yet.
In the paper
“An intermediate in this pathway, xylulose-5-phosphate, activates ChREBP (1) and promotes its binding to the carbohydrate response element sites in the promoters of target genes, including FGF21 (53, 130).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Regulation of Macronutrient Intake and Sweet Taste Preference by FGF21
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This study found that FGF21 was elevated robustly by low protein and that this induction was maximized when low-protein intake was coupled with high-carbohydrate intake (121).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Regulation of Macronutrient Intake and Sweet Taste Preference by FGF21
What the sources say
- Not checked yetcites [121] 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
“Notably, without affecting protein levels, excess carbohydrate led to an approximately eightfold increase in circulating FGF21 levels, an effect not observed with increased fat intake (84).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Regulation of Macronutrient Intake and Sweet Taste Preference by FGF21
What the sources say
- Not checked yetcites [84] 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.
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
“Together, these data reveal that FGF21 is induced in response to excess levels of carbohydrate and that the loss of FGF21 signaling increases carbohydrate preference.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Regulation of Macronutrient Intake and Sweet Taste Preference by FGF21
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
“Since FGF21 administration increases energy expenditure and the browning of adipose tissues in vivo (21, 64, 141), it was hypothesized that FGF21 regulates adaptive thermogenesis in response to cold.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21 and Adaptive Thermogenesis
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 addition, treating human primary neck adipocytes with FGF21 increases both thermogenic gene expression and cellular respiration (76).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21 and Adaptive Thermogenesis
What the sources say
- Not checked yetcites [76] 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
“Consistent with the earlier studies, while FGF21 significantly increased insulin sensitivity in both lean and diet-induced obese wild-type mice, this effect was completely lost in Klbfl/fl;Adiponectin-Cre mice (11).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 Signals to Adipose Tissues to Acutely Increase Insulin Sensitivity
What the sources say
- Not checked yetcites [11] 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
“Importantly, in animal models FGF21 treatment not only prevents (64) but also reverses diabetes and obesity (21, 141).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21
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
“For example, while chronic feeding of a high-fat diet clearly represents a state of cellular and mitochondrial stress for skeletal muscle, skeletal muscle does not contribute to circulating levels of FGF21 during feeding of a high-fat diet; instead, circulating levels of FGF21 are derived exclusively from the liver under these conditions (86).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Induction of FGF21 by Cellular and Mitochondrial Stress
What the sources say
- Not checked yetcites [86] source
boosted- 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
“In contrast to the acute metabolic effects, repeated daily administration of FGF21 increases metabolic rate, promotes weight loss, and thus secondarily improves insulin sensitivity and glucose homeostasis (141).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21
What the sources say
- Not checked yetcites [141] 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
“When administered to diabetic and obese animal models, FGF21 provides multiple metabolic benefits and has been shown to decrease blood glucose levels and body weight, improve insulin and leptin sensitivity, improve plasma lipid profiles, and decrease hepatic steatosis (21, 64, 141, 142).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The acute pharmacological administration of FGF21 increases insulin sensitivity and lowers plasma glucose levels, primarily by stimulating peripheral glucose disposal, while also slightly reducing hepatic glucose production (27, 142).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 Signals to Adipose Tissues to Acutely Increase Insulin Sensitivity
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
“Consistent with a functional role for FGF21 during cold, both Fgf21 total knockout mice (36) and adipose-specific Fgf21 knockout mice (52) exhibit reduced body temperature in response to acute cold exposure.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > FGF21 and Adaptive Thermogenesis
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
“Although FGF21 is induced under conditions of metabolic stress (e.g., fasting, cold), it is also induced under many conditions of cellular stress, leading FGF21 to be referred to in some contexts as a stress hormone (69).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHYSIOLOGICAL EFFECTS OF FGF21 > Induction of FGF21 by Cellular and Mitochondrial Stress
What the sources say
- Not checked yetcites [69] 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, in contrast to previous studies, both FGF21 (11) and a bispecific activating antibody for the FGFR1–β-klotho receptor complex (70) were found to efficiently retain their acute insulin-sensitizing effects in adiponectin knockout mice (Figure 4).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 Signals to Adipose Tissues to Acutely Increase Insulin Sensitivity
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
“Extended FGF21 administration increases energy expenditure, promotes lipid and glucose uptake in BAT, and increases adipose tissue metabolism (88).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 and the Central Nervous System
What the sources say
- Not checked yetcites [88] 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
“FGF21 crosses the blood–brain barrier and acts centrally to regulate multiple processes (50).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 and the Central Nervous System
What the sources say
- Not checked yetcites [50] 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
“Increased insulin sensitization in adipose tissues results in increased glucose uptake in BAT (11) and attenuation of lipolysis in WAT (5).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 Signals to Adipose Tissues to Acutely Increase Insulin Sensitivity
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, FGF21 enhances insulin sensitivity in primary brown adipocytes (86) but not in primary white adipocytes (64, 86).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 Signals to Adipose Tissues to Acutely Increase Insulin Sensitivity
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
“Consistent with recombinant FGF21 administration, the administration of a bispecific FGFR1–β-klotho agonist to diet-induced obese wild-type mice promotes weight loss and improves glucose homeostasis, effects that are lost when β-klotho is removed from the CNS (74).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 and the Central Nervous System
What the sources say
- Not checked yetcites [74] 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
“FGF21 administration increases sympathetic nerve activity to BAT (101) and WAT (28), and browning of WAT depots (28, 101).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 and the Central Nervous System
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
“Positron emission tomography and computed tomography imaging revealed that acute administration of FGF21 with insulin markedly induced glucose uptake in interscapular BAT compared to insulin alone, and this effect is impaired in mice lacking β-klotho in BAT (11).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 Signals to Adipose Tissues to Acutely Increase Insulin Sensitivity
What the sources say
- Not checked yetcites [11] 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
“While lipodystrophic mice do not respond to FGF21 administration, the transplantation of WAT from wild-type mice increases leptin levels and restores FGF21 responsiveness (131).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > FGF21 and the Central Nervous System
What the sources say
- Not checked yetcites [131] 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
“However, a separate study suggests that this phenotype is due to caloric insufficiency from chronic energy expenditure (119).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > TRANSLATING THE METABOLIC EFFECTS OF FGF21
What the sources say
- Not checked yetcites [119] source
hedgeddirect- Asserted: fails — The authors may not 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 authors may not put it forward as true. The paper’s conclusions may not depend on it.
In the paper
“When PF-05231023 was administered to obese cynomolgus monkeys, it decreased body weight and mean abdominal fat content but did not affect bone mineral content (126).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > TRANSLATING THE METABOLIC EFFECTS OF FGF21
What the sources say
- Not checked yetcites [126] 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
“Although circulating levels of FGF21 are derived from the liver, adipose-derived circulating microRNAs are packaged into exosomes and regulate plasma FGF21 levels (129).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > Mechanisms Regulating FGF21 Activity
What the sources say
- Not checked yetcites [129] 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.
None of the sources cited for this claim have been checked yet.
In the paper
“In mice, FGF21 has been reported to promote bone loss (134, 135); however, this finding could not be replicated (80).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > TRANSLATING THE METABOLIC EFFECTS OF FGF21
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
“Similar to the previous study (126), once-weekly administration of PF-05231023 markedly improved plasma lipid profiles without significantly affecting fasting plasma glucose levels (66).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > TRANSLATING THE METABOLIC EFFECTS OF FGF21
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
“While Fgf21 transgenic mice are infertile on a chow diet, this infertility is reversed by high-fat diet feeding (119).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > TRANSLATING THE METABOLIC EFFECTS OF FGF21
What the sources say
- Not checked yetcites [119] 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
“One study found that FGF21 signals to the brain to suppress vasopressin–kisspeptin signaling, which impairs the proestrus surge in luteinizing hormone (100).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > TRANSLATING THE METABOLIC EFFECTS OF FGF21
What the sources say
- Not checked yetcites [100] 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. It may state two separate claims as one.
In the paper
“However, the concept of FGF21 resistance is controversial, with another group failing to observe FGF21 resistance in mouse models of obesity and insulin resistance (45).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > Mechanisms Regulating FGF21 Activity
What the sources say
- Not checked yetcites [45] 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.
In the paper
“Notably, this FGF21 analog also significantly reduced body weight and metabolic profiles in nonhuman primates, but did so by reducing their food intake rather than by increasing the browning of subcutaneous WAT (126).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > TRANSLATING THE METABOLIC EFFECTS OF FGF21
What the sources say
- Not checked yetcites [126] 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
“The majority of adverse effects were gastrointestinal, but unlike the previous study, systolic and diastolic blood pressure, and pulse rate, increased in a dose-dependent manner (66).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > TRANSLATING THE METABOLIC EFFECTS OF FGF21
What the sources say
- Not checked yetcites [66] 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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In addition, FGF21 regulates macronutrient preference, sweet taste preference, and alcohol intake through central mechanisms.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > CONCLUSIONS
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
“Administering this analog for 28 days resulted in decreased body weight, improved lipid profiles, lowered fasting insulin levels, and a trend toward reduced plasma glucose levels (41).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > TRANSLATING THE METABOLIC EFFECTS OF FGF21
What the sources say
- Not checked yetcites [41] source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Circulating human FGF21 is composed of 181 amino acids and is proteolytically cleaved, and inactivated, between Pro-171 and Ser-172 by the endopeptidase fibroblast activation protein (FAP) (29, 150).”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > THE PHARMACOLOGICAL EFFECTS OF FGF21 > Mechanisms Regulating FGF21 Activity
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In the same study, PF-05231023 did not affect systolic or diastolic blood pressure, pulse rate, or electrocardiogram readings.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > TRANSLATING THE METABOLIC EFFECTS OF FGF21
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- Not checked yetcites [126] source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“PF-05231023 significantly decreased body weight and markedly reduced plasma cholesterol and lipid levels.”
§ Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis > TRANSLATING THE METABOLIC EFFECTS OF FGF21
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- Not checked yetcites [126] source
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper relies on this without support.
Humans possess relatively less BAT than rodents.
“Since humans possess relatively less BAT than rodents, adipose tissue thermogenesis may contribute less to overall energy homeostasis in humans.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“As a non-canonical fibroblast growth factor, fibroblast growth factor 21 (FGF21) functions as an endocrine hormone that signals to distinct targets throughout the body.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [3]
In the citing paper
“prolonged administration of FGF21 or FGF21 analogues has important metabolic effects, including a marked decrease in body weight in rodents and non-human primates, and more modest effects on body weight in humans3,40,58,77,78.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [3]
In the citing paper
“Physiological circulating levels of FGF21 are produced primarily by the liver in response to homeostatic imbalance, perhaps partly to protect the liver itself from metabolic or cellular stress3,104.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [3]
In the citing paper
“Because circulating levels of FGF21 are significantly elevated during obesity and diabetes3, and given the known metabolic effects of FGF21, FGF21’s action might logically be reasoned to somehow be impaired, or ‘FGF21 resistant’, during obesity37.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [3]
In the citing paper
“making it a marker for metabolic disorders [141] (Table 1).”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [141]
In the citing paper
“FGF21's metabolic effects are achieved through actions on different tissues [141].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [141]
In the citing paper
“this increase in circulating FGF21 levels may reflect impaired endocrine signaling that results in FGF21 resistance, similar to insulin or leptin resistance [141] (Figure 3).”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [141]
In the citing paper
“Altogether, FGF21 seems to serve as a protective factor that limits hepatic toxicity [141,167] and dysfunction [168].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [141]
In the citing paper
“Collectively, these data provide compelling evidence that FGF21 acts directly in the brain to suppress both sweet and alcohol consumption and preference”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [125]
In the citing paper
“It is worth noting that FGF21 knockout mice exhibit lower glycemia in the fasted state, and lower plasma levels of ketone bodies in both the fasted and the fed state 64, 65.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [64]
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Cellular Mechanisms by Which FGF21 Improves Insulin Sensitivity in Male Mice
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Sweet Sixteenth for ChREBP: Established Roles and Future Goals
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FGF21 contributes to neuroendocrine control of female reproduction
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“For example, FGF21 production from skeletal muscle (56, 61, 103, 128), BAT (59), and cardiac tissue (143) is increased in genetic mouse models of cellular or mitochondrial stress.”
BackgroundFGF21 is a biomarker for mitochondrial translation and mtDNA maintenance disorders
Lehtonen, J. M., Forsström, S., Bottani, E., Viscomi, C., Baris, O. R., Isoniemi, H., Höckerstedt, K., Österlund, P., Hurme, M., Jylhävä, J., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000003374 · Cited by 220
FGF21 Is a Sugar-Induced Hormone Associated with Sweet Intake and Preference in Humans
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Self-citationCentral Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice
Douris, N., Stevanovic, D. M., Fisher, F. M., Cisu, T. I., Chee, M. J., Nguyen, N. L., Zarebidaki, E., Adams, A. C., Kharitonenkov, A., Flier, J. S., et al. (2015) · Endocrinology · doi:10.1210/en.2014-2001 · Cited by 215
FGF21 and the late adaptive response to starvation in humans
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“Consistent with data from rodents, circulating levels of FGF21 are also induced in humans during prolonged fasting (33, 42).”
BackgroundDefining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework
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OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance
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Pharmacologic Effects of FGF21 Are Independent of the “Browning” of White Adipose Tissue
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Metabolic Pitfalls of CNS Cre-Based Technology
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Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease
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Novel locus including FGF21 is associated with dietary macronutrient intake
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Glucose induces FGF21 mRNA expression through ChREBP activation in rat hepatocytes
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Lack of Overt FGF21 Resistance in Two Mouse Models of Obesity and Insulin Resistance
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FGF21 Requires βklotho to Act In Vivo
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Beneficial effects of ketogenic diet in obese diabetic subjects
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A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution
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Dietary Fructose and Glucose Differentially Affect Lipid and Glucose Homeostasis
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A critical role for ChREBP-mediated FGF21 secretion in hepatic fructose metabolism
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“Mice lacking ChREBP fail to show an increase in plasma FGF21 levels in response to simple sugar intake (35, 133).”
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FGF21-based pharmacotherapy – potential utility for metabolic disorders
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Fibroblast Activation Protein Cleaves and Inactivates Fibroblast Growth Factor 21
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Discrete Aspects of FGF21 In Vivo Pharmacology Do Not Require UCP1
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“Importantly, it is unclear whether there is any translational relevance of FGF21 to the beneficial effects of ketogenic diets in humans because circulating FGF21 levels fail to increase in humans in response to a ketogenic diet (19, 42, 73).”
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FGF21 N‐ and C‐termini play different roles in receptor interaction and activation
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Different roles of N‐ and C‐ termini in the functional activity of FGF21
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Fibroblast Growth Factor 21 Improves Insulin Resistance and Ameliorates Renal Injury in db/db Mice
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FGF21 Promotes Metabolic Homeostasis via White Adipose and Leptin in Mice
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Co-receptor Requirements for Fibroblast Growth Factor-19 Signaling
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Genetics of Food Intake and Eating Behavior Phenotypes in Humans
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A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response
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Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates
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Glucagon-to-insulin ratio is pivotal for splanchnic regulation of FGF-21 in humans
Hansen, J. S., Clemmesen, J. O., Secher, N. H., Hoene, M., Drescher, A., Weigert, C., Pedersen, B. K., & Plomgaard, P. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.06.001 · Cited by 123
FGF21 mediates the lipid metabolism response to amino acid starvation
De Sousa-Coelho, A. L., Relat, J., Hondares, E., Pérez-Martí, A., Ribas, F., Villarroya, F., Marrero, P. F., & Haro, D. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m033415 · Cited by 123
Circulating FGF21 proteolytic processing mediated by fibroblast activation protein
Zhen, E. Y., Jin, Z., Ackermann, B. L., Thomas, M. K., & Gutierrez, J. A. (2016) · Biochemical Journal · doi:10.1042/bj20151085 · Cited by 123
Long-Term Cold Adaptation Does Not Require FGF21 or UCP1
Keipert, S., Kutschke, M., Ost, M., Schwarzmayr, T., van Schothorst, E. M., Lamp, D., Brachthäuser, L., Hamp, I., Mazibuko, S. E., Hartwig, S., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.016 · Cited by 122
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Fundamentals of FGF19 & FGF21 Action In Vitro and In Vivo
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Protein-dependent regulation of feeding and metabolism
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Metabolic fibroblast growth factors (FGFs): Mediators of energy homeostasis
Markan, K. R., & Potthoff, M. J. (2016) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2015.09.021 · Cited by 103
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Fibroblast growth factor 21 night watch: advances and uncertainties in the field
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The Structural Biology of the FGF19 Subfamily
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Fibroblast activation protein (FAP) as a novel metabolic target
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FGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue
Markan, K. R., Naber, M. C., Small, S. M., Peltekian, L., Kessler, R. L., & Potthoff, M. J. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.03.009 · Cited by 70
Self-citationFGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans
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A new frontier in FGF21 biology
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Fgf21 Impairs Adipocyte Insulin Sensitivity in Mice Fed a Low-Carbohydrate, High-Fat Ketogenic Diet
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Fibroblast growth factor 21 has no direct role in regulating fertility in female mice
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Elevated Serum Fibroblast Growth Factor 21 in Humans with Acute Pancreatitis
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FAP finds FGF21 easy to digest
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Metadata
- Authors
- BonDurant, L. D., & Potthoff, M. J.
- Affiliations
- University of Iowa (US)
- ORCID
- Potthoff, Matthew J.
- Venue
- Annual Review of Nutrition
- Publisher
- Annual Reviews
- Published
- 2018-08-21
- Volume
- 38
- Issue
- 1
- Pages
- 173-196
- ISSN
- 0199-9885 (ISSN-L)
- 1545-4312
- PMC
- PMC6964258
- OpenAlex
- W2799463911
- Semantic Scholar
- 6a834338b1ae9b0e4c5e4a258c3655658f646629
- Cited by
- 222
- References
- 152
- Citations by year
- 2026: 25 · 2025: 25 · 2024: 29 · 2023: 33 · 2022: 30 · 2021: 34 · 2020: 18 · 2019: 25 · 2018: 3
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Roy J. and Lucille A. Carver College of Medicine, University of Iowa
- National Institute of General Medical Sciences (T32GM067795)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK106104)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Peptidase Inhibition and Analysis
- Keywords
- FGF21, metabolic homeostasis, liver, nutrient sensing, nutrient homeostasis, diabetes mellitus, obesity, metabolic disease treatment
- MeSH terms
- Ethanol, Animals, Fibroblast Growth Factors, Food Deprivation, Gene Expression Regulation, Homeostasis, Humans, Lipid Metabolism
About these checks
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.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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