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Fibroblast Growth Factor 21 Corrects Obesity in Mice
Abstract
Fibroblast growth factor 21 (FGF21) is a metabolic regulator that provides efficient and durable glycemic and lipid control in various animal models. However, its potential to treat obesity, a major health concern affecting over 30% of the population, has not been fully explored. Here we report that systemic administration of FGF21 for 2 wk in diet-induced obese and ob/ob mice lowered their mean body weight by 20% predominantly via a reduction in adiposity. Although no decrease in total caloric intake or effect on physical activity was observed, FGF21-treated animals exhibited increased energy expenditure, fat utilization, and lipid excretion, reduced hepatosteatosis, and ameliorated glycemia. Transcriptional and blood cytokine profiling studies revealed effects consistent with the ability of FGF21 to ameliorate insulin and leptin resistance, enhance fat oxidation and suppress de novo lipogenesis in liver as well as to activate futile cycling in adipose. Overall, these data suggest that FGF21 exhibits the therapeutic characteristics necessary for an effective treatment of obesity and fatty liver disease and provides novel insights into the metabolic determinants of these activities.
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“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 [77]
In the citing paper
“Pharmacological administration of FGF21 to obese rodents reverses diabetes and obesity through increasing energy expenditure77,78.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [77]
In the citing paper
“Pharmacological administration of FGF21 decreases plasma glucose and lipid levels, improves insulin and leptin sensitivity, decreases hepatic steatosis, increases energy expenditure [[131], [132], [133], [134], [135], [136]], and decreases sugar and alcohol intake in mice [[137], [138], [139], [140], [141], [142]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [131]
In the citing paper
“Pharmacological administration of FGF21 decreases plasma glucose and lipid levels, improves insulin and leptin sensitivity, decreases hepatic steatosis, increases energy expenditure [[131], [132], [133], [134], [135], [136]], and decreases sugar and alcohol intake in mice [[137], [138], [139], [140], [141], [142]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [131]
In the citing paper
“Pharmacological administration of FGF21 decreases plasma glucose and lipid levels, improves insulin and leptin sensitivity, decreases hepatic steatosis, increases energy expenditure [[131], [132], [133], [134], [135], [136]], and decreases sugar and alcohol intake in mice [[137], [138], [139], [140], [141], [142]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [131]
In the citing paper
“Pharmacological administration of FGF21 decreases plasma glucose and lipid levels, improves insulin and leptin sensitivity, decreases hepatic steatosis, increases energy expenditure [[131], [132], [133], [134], [135], [136]], and decreases sugar and alcohol intake in mice [[137], [138], [139], [140], [141], [142]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [131]
In the citing 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).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [21]
In the citing 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).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [21]
In the citing paper
“Importantly, in animal models FGF21 treatment not only prevents (64) but also reverses diabetes and obesity (21, 141).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [21]
In the citing 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.”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [21]
In the citing paper
“It is clear that FGF21 treatment elicits significant metabolic changes in many tissues, including the liver and adipose tissues (21, 141).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [21]
In the citing paper
“FGF21’s ability to reduce body weight, glucose levels, and lipid concentrations in models of obesity generated substantial initial interest”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [116]
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Metadata
- Authors
- Coskun, T., Bina, H. A., Schneider, M. A., Dunbar, J. D., Hu, C. C., Chen, Y., Moller, D. E., & Kharitonenkov, A.
- Affiliations
- Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285
- Eli Lilly (United States) (US)
- Corresponding author
- Kharitonenkov, Alexei
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2008-08-07
- Volume
- 149
- Issue
- 12
- Pages
- 6018-6027
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2114650931
- Cited by
- 1,031
- References
- 26
- Citations by year
- 2026: 17 · 2025: 34 · 2024: 58 · 2023: 63 · 2022: 57 · 2021: 72 · 2020: 67 · 2019: 76 · 2018: 72 · 2017: 64 · 2016: 78 · 2015: 85 · 2014: 71 · 2013: 62 · 2012: 61
- FWCI
- 12.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- FGF21, obesity, diet-induced obesity, ob/ob mice, energy expenditure, fat oxidation, de novo lipogenesis, hepatic steatosis, insulin resistance, leptin resistance, glycemia, lipid excretion, adipose tissue, metabolic therapy
- MeSH terms
- Animals, Body Weight, Energy Intake, Dietary Fats, Energy Metabolism, Fibroblast Growth Factors, Insulin, Insulin Resistance, Male, Mice, Inbred C57BL, Motor Activity, Obesity, Leptin, Adiposity, Mice
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