Related Experiment Video
Updated: May 20, 2026
Body Composition and Metabolic Caging Analysis in High Fat Fed Mice
Published on: May 24, 2018
FGF21 promotes metabolic homeostasis via white adipose and leptin in mice
Murielle M Véniant1, Clarence Hale, Joan Helmering
1Department of Metabolic Disorders, Amgen Inc., Thousand Oaks, California, United States of America.
Abstract:
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.
Insights
Adipose tissue is essential for Fibroblast Growth Factor 21 (FGF21) to lower glucose and triglycerides. Restoring adipose tissue or adding leptin regained FGF21
Area of Science:
- Metabolic Regulation
- Endocrinology
- Molecular Biology
Background:
- Fibroblast Growth Factor 21 (FGF21) is a key metabolic regulator.
- Pharmacological FGF21 administration lowers glucose and lipids in mammals.
- The role of adipose tissue in FGF21's anti-diabetic effects requires clarification.
Purpose of the Study:
- To determine if adipose tissue is the primary organ mediating the anti-diabetic effects of FGF21.
- To investigate the impact of adipose mass on FGF21 responsiveness.
- To explore the interplay between leptin and FGF21 in metabolic regulation.
Main Methods:
- Treatment of lipodystrophy mice (Tg) with reduced body fat using recombinant murine FGF21 (rmuFGF21).
- White adipose tissue (WAT) transplantation from wildtype (WT) mice into Tg mice.
- Assessment of FGF21 responsiveness, glucose tolerance, and molecular signaling pathways.
Main Results:
- Tg mice were unresponsive to rmuFGF21's beneficial effects on body weight, adipose mass, insulin, and glucose tolerance.
- WAT transplantation into Tg mice completely restored FGF21 responsiveness.
- Leptin treatment alone rescued the anti-diabetic effects of rmuFGF21 in Tg mice.
- Adipose tissue in Tg mice showed resistance to FGF21 signaling, while liver signaling remained normal.
Conclusions:
- Adipose tissue is critical for FGF21's triglyceride and glucose-lowering effects, but not cholesterol reduction.
- Leptin and FGF21 exhibit additive anti-diabetic actions.
- These findings highlight adipose tissue as a key mediator of FGF21's metabolic benefits.
