Language

English

Publication Date

7-1-2025

Journal

Cell Metabolism

DOI

10.1016/j.cmet.2025.05.011

PMID

40527315

PMCID

PMC12221793

PubMedCentral® Posted Date

6-16-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Approximately 35% of US adults over 65 are obese, highlighting the need for therapies targeting age-related metabolic issues. Fibroblast growth factor 21 (FGF21), a hormone mainly produced by the liver, improves metabolism and extends lifespan. To explore its effects without developmental confounders, we generated mice with adipocyte-specific FGF21 overexpression beginning in adulthood. When fed a high-fat diet, these mice lived up to 3.3 years, resisted weight gain, improved insulin sensitivity, and showed reduced liver steatosis. Aged transgenic mice also displayed lower levels of inflammatory immune cells and lipotoxic ceramides in visceral adipose tissue, benefits that occurred even in the absence of adiponectin, a hormone known to regulate ceramide breakdown. These results suggest that fat tissue is a central site for FGF21's beneficial effects and point to its potential for treating metabolic syndrome and age-related diseases by promoting a healthier metabolic profile under dietary stress and extending healthspan and lifespan.

Keywords

Animals, Fibroblast Growth Factors, Obesity, Longevity, Diet, High-Fat, Mice, Mice, Transgenic, Male, Mice, Inbred C57BL, Insulin Resistance, Adiponectin, Fatty Liver, Liver, Ceramides, Adipocytes, Adipocytes, Adipose tissue, FGF21, Aging, Longevity, Ceramides, Obesity, Insulin sensitivity, Adiponectin, Inflammation

Published Open-Access

yes

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