FGF21 Promotes Metabolic Homeostasis via White Adipose and Leptin in Mice
Open accessAbstract
Fibroblast growth factor 21 (FGF21) is a potent metabolic regulator, and pharmacological administration elicits glucose and lipid lowering responses in mammals. To delineate if adipose tissue is the predominant organ responsible for anti-diabetic effects of FGF21, we treated mice with reduced body fat (lipodystrophy mice with adipose specific expression of active sterol regulatory element binding protein 1c; Tg) with recombinant murine FGF21 (rmuFGF21). Unlike wildtype (WT) mice, Tg mice were refractory to the beneficial effects of rmuFGF21 on body weight, adipose mass, plasma insulin and glucose tolerance. To determine if adipose mass was critical for these effects, we transplanted WT white adipose tissue (WAT) into Tg mice and treated the mice with rmuFGF21. After transplantation, FGF21 responsiveness was completely restored in WAT transplanted Tg mice compared to sham Tg mice. Further, leptin treatment alone was sufficient to restore the anti-diabetic effects of rmuFGF21 in Tg mice. Molecular analyses of Tg mice revealed normal adipose expression of Fgfr1, Klb and an 8-fold over-expression of Fgf21. Impaired FGF21-induced signaling indicated that residual adipose tissue of Tg mice was resistant to FGF21, whilst normal FGF21 signaling was observed in Tg livers. Together these data suggest that adipose tissue is required for the triglyceride and glucose, but not the cholesterol lowering efficacy of FGF21, and that leptin and FGF21 exert additive anti-diabetic effects in Tg mice.
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Transplantation of WAT from wild-type mice increases leptin levels and restores FGF21 responsiveness in lipodystrophic mice.
“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).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [131]
Lipodystrophic mice, which lack mature adipocytes, are refractory to the metabolic effects of FGF21 and FGFR1-based agonists.
“Lipodystrophic mice, which lack mature adipocytes, are refractory to the metabolic effects of FGF21 (131) and FGFR1-based agonists (38).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [131]
FGF21 administration enhances leptin-mediated decreases in body weight.
“Finally, FGF21 administration enhances leptin-mediated decreases in body weight (96, 131).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [131]
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- Authors
- Véniant, M. M., Hale, C., Helmering, J., Chen, M. M., Stanislaus, S., Busby, J., Vonderfecht, S., Xu, J., & Lloyd, D. J.
- Affiliations
- Amgen (United States) (US)
- Corresponding author
- Lloyd, David J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-07-06
- Volume
- 7
- Issue
- 7
- Pages
- e40164
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3391219
- OpenAlex
- W2046402204
- Cited by
- 141
- References
- 28
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 9 · 2022: 7 · 2021: 11 · 2020: 9 · 2019: 10 · 2018: 7 · 2017: 12 · 2016: 21 · 2015: 14 · 2014: 12 · 2013: 12 · 2012: 7
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Amgen
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- FGF21, white adipose tissue, leptin, lipodystrophy, SREBP-1c, adipose tissue transplantation, glucose tolerance, insulin resistance, metabolic homeostasis, FGF receptor 1, KLB, anti-diabetic effects, triglyceride lowering, cholesterol lowering
- MeSH terms
- Animals, Disease Models, Animal, Female, Fibroblast Growth Factors, Gene Expression Regulation, Glucose, Homeostasis, Humans, Lipodystrophy, Male, Mice, Transgenic, Recombinant Proteins, Signal Transduction, Leptin, PPAR gamma, Mice, Receptor, Fibroblast Growth Factor, Type 1, Adipose Tissue, White
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