Increased Fibroblast Growth Factor 21 in Obesity and Nonalcoholic Fatty Liver Disease
Open accessAbstract
Background & aims Fibroblast growth factor 21 (FGF21) is an hepatic protein that plays a critical role in metabolism, stimulating fatty acid oxidation in liver and glucose uptake in fat. Systemic administration to obese rodents and diabetic monkeys leads to improved glucose homeostasis and weight loss. In rodents, FGF21 increases with fasting and consumption of a ketogenic diet (KD). In humans, FGF21 correlates with body mass index (BMI), but studies evaluating other parameters show inconsistent results. We examined FGF21 serum levels in lean and obese individuals and in response to dietary manipulation. We also evaluated FGF21 serum levels and liver messenger RNA (mRNA) expression in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).Methods Serum FGF21 was measured after an overnight fast in individuals with BMI ranging from normal to obese. Volunteers fasted for 16 or 72 hours and then ate a standard meal. Another group consumed KD for 12 days. Serum FGF21 and hepatic mRNA expression were measured in obese individuals with NAFLD or NASH.Results There was a positive correlation between BMI and FGF21. There was no change in FGF21 in response to a short fast or KD. A nonstatistically significant fall in FGF21 levels was seen after a 72-hour fast. Hepatic FGF21 mRNA expression was significantly elevated in NAFLD, which correlated with a substantial increase in serum FGF21. In NASH, serum FGF21 but not liver mRNA was increased.Conclusions FGF21 correlates with BMI and may be a novel biomarker for NAFLD, but is not nutritionally regulated in humans.
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FGF21 levels increase in patients with obesity, which might represent a state of FGF21 resistance.
“Paradoxically, FGF21 levels increase in patients with obesity [153], which might represent a state of FGF21 resistance [154].”
When administered to mice at 10 g/kg, exendin-4 effectively suppressed the binding activity of NF-Bp65 in individuals with T2D, and after 48 weeks of therapy, activation of NF-κB was reduced.
“When administered to mice at 10 g/kg, exendin-4 effectively suppressed the binding activity of NF-Bp65 in individuals with T2D, and after 48 weeks of therapy, activation of NF-κB was reduced.”
From Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications (2024) · cites this paper as [40]
The Introduction and Discussion describe FGF21 and its metabolic effects, not exendin-4. Searches for exendin-4, NF-κB/p65 binding activity, the stated dose, and 48 weeks of therapy found no passage addressing the claimed effect; the cited paper therefore cannot verify it. (LLM, conf=0.78)
Experimental — accuracy not yet measuredBoth the serum FGF21 level and liver FGF21 mRNA level are increased in MAFLD patients, and the level of IGFBP1 increases and serves as an independent predictor of hepatic steatosis.
“In contrast, both the serum FGF21 level and liver FGF21 mRNA level is increased in MAFLD patients as long as the level of IGFBP1 increases and serves as an independent predictor of hepatic steatosis [130,131].”
From Emerging role of liver-bone axis in osteoporosis (2024) · cites this paper as [130]
The effect of fasting and ketogenic diets to increase FGF21 is not nearly as robust in humans as initially observed in mice.
“The effect of fasting and ketogenic diets to increase FGF21 is not nearly as robust in humans as initially observed in mice”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [132]
FGF21 is increased in settings of obesity.
“FGF21 is also increased in settings of obesity”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [132]
FGF21 has been directly linked to metabolic stress and liver steatosis.
“FGF21 has been directly linked to metabolic stress and liver steatosis”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [132]
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- Authors
- Dushay, J., Chui, P. C., Gopalakrishnan, G. S., Varela–Rey, M., Crawley, M., Fisher, F. M., Badman, M. K., Martinez–Chantar, M. L., & Maratos–Flier, E.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Maratos–Flier, Eleftheria
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 139
- Issue
- 2
- Pages
- 456-463
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC4862867
- OpenAlex
- W2005063766
- Cited by
- 607
- References
- 28
- Citations by year
- 2026: 27 · 2025: 30 · 2024: 34 · 2023: 42 · 2022: 41 · 2021: 40 · 2020: 48 · 2019: 42 · 2018: 38 · 2017: 38 · 2016: 55 · 2015: 42 · 2014: 37 · 2013: 29 · 2012: 34
- FWCI
- 11.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01dk069983-05)
- U.S. Public Health Service (SAF2005-00855)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK056116, P30DK046200, 5R01DK069983-04, R01-DK-069983, 5P01DK056106-10, DK46200.)
- National Center for Research Resources (M01-RR-01032, M01RR001032)
- National Center for Complementary and Integrative Health (R01AT001576, AT-1576)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- FGF21, obesity, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, body mass index, fasting, ketogenic diet, serum biomarkers, hepatic metabolism
- MeSH terms
- Adult, Fasting, Fatty Liver, Female, Fibroblast Growth Factors, Humans, Liver, Male, Nutritional Status, Obesity, Prospective Studies, RNA, Messenger, Time Factors, Biomarkers, Up-Regulation, Body Mass Index, Adipose Tissue, White, Diet, Ketogenic, Young Adult
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