ArticleThe Journal of clinical investigation2015
FGF21 and the late adaptive response to starvation in humans.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
136 citing papers in PubMed, 210 citations in OpenAlex.
- Trial
- LLF580, an FGF21 Analog, Reduces Triglycerides and Hepatic Fat in Obese Adults With Modest Hypertriglyceridemia.The Journal of clinical endocrinology and metabolism · 2022Trial
- Short Term Isocaloric Ketogenic Diet Modulates NLRP3 InflammasomeFrontiers in immunology · 2022Trial
- Validation of the Micronutrient and Environmental Enteric Dysfunction Assessment Tool and evaluation of biomarker risk factors for growth faltering and vaccine failure in young Malian children.PLoS neglected tropical diseases · 2020Trial
- Effects of beta-conglycinin intake on circulating FGF21 levels and brown adipose tissue activity in Japanese young men: a single intake study and a randomized controlled trial.Journal of physiological anthropology · 2020Trial
- The effect of hydration status on plasma FGF21 concentrations in humans: A subanalysis of a randomised crossover trial.PloS one · 2020Trial
- Plasma FGF21 levels in obese patients undergoing energy-restricted diets or bariatric surgery: a marker of metabolic stress?International journal of obesity (2005) · 2017Trial
- High-Protein Intake during Weight Loss Therapy Eliminates the Weight-Loss-Induced Improvement in Insulin Action in Obese Postmenopausal Women.Cell reports · 2016Trial
- Trial
- Increasing autophagy with fasting and diet: separating fact from fiction.Biochemical Society transactions · 2026Review
- Fetuin-b Mediates Lipid Overload-Induced Hepatic Lipid Accumulation in Large Yellow Croaker (Larimichthys crocea).FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Investigating fasting for metabolic health and longevity.Biogerontology · 2026Review
- The carrying capacity for free fatty acids in plasma is exceedingly high in mammals, and this may be a liability for human metabolic health.The Journal of physiology · 2026Article
- Dietary restriction in aging and longevity.Nature aging · 2026Review
- Effect of Muscle Contraction Under Caloric Restriction on Irisin and FGF21 Secretion in Mice.Physiological research · 2025Article
- The Metabolic Transition Between Fasting and Feeding Alters Aging-Associated Metabolites, Lowers BCAAs, and Stimulates FGF21 Production in Humans.Aging cell · 2025Article
- A Critical Assessment of Fasting to Promote Metabolic Health and Longevity.Endocrine reviews · 2025Review
- Decision-Making Scores and Hunger Susceptibility: A Positive Correlation Mediated by Fasting FGF21 Independently of Body Fat.Nutrients · 2025Article
- Sex Differences in Ketogenic Diet Response Reveal Gonadal Hormone Interaction With FGF21 in Mice.Journal of the Endocrine Society · 2025Article
- Prolonged Water-Only Fasting Followed by a Whole-Plant-Food Diet Promotes Fat-Free Mass Recovery and Continued Fat Mass Loss in Adults With Overweight or Obesity.Obesity science & practice · 2025Article
76 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
In mice, FGF21 is rapidly induced by fasting, mediates critical aspects of the adaptive starvation response, and displays a number of positive metabolic properties when administered pharmacologically. In humans, however, fasting does not consistently increase FGF21, suggesting a possible evolutionary divergence in FGF21 function. Moreover, many key aspects of FGF21 function in mice have been identified in the context of transgenic overexpression or administration of supraphysiologic doses, rather than in a physiologic setting. Here, we explored the dynamics and function of FGF21 in human volunteers during a 10-day fast. Unlike mice, which show an increase in circulating FGF21 after only 6 hours, human subjects did not have a notable surge in FGF21 until 7 to 10 days of fasting. Moreover, we determined that FGF21 induction was associated with decreased thermogenesis and adiponectin, an observation that directly contrasts with previous reports based on supraphysiologic dosing. Additionally, FGF21 levels increased after ketone induction, demonstrating that endogenous FGF21 does not drive starvation-mediated ketogenesis in humans. Instead, a longitudinal analysis of biologically relevant variables identified serum transaminases--markers of tissue breakdown--as predictors of FGF21. These data establish FGF21 as a fasting-induced hormone in humans and indicate that FGF21 contributes to the late stages of adaptive starvation, when it may regulate the utilization of fuel derived from tissue breakdown.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.