Prolonged FGF21 treatment increases energy expenditure and induces weight loss in obese mice independently of UCP1 and adrenergic signaling

0584426 - FGÚ 2025 RIV GB eng J - Journal Article
Stanić, Sara - Bardová, Kristina - Janovská, Petra - Rossmeisl, Martin - Kopecký, Jan - Zouhar, Petr
Prolonged FGF21 treatment increases energy expenditure and induces weight loss in obese mice independently of UCP1 and adrenergic signaling.
Biochemical Pharmacology. Roč. 221, March (2024), č. článku 116042. ISSN 0006-2952. E-ISSN 1873-2968
R&D Projects: GA ČR(CZ) GJ19-05356Y; GA MŠMT(CZ) LX22NPO5104
Institutional support: RVO:67985823
Keywords : fibroblast growth factor 21 * energy expenditure * weight loss * brown adipose tissue * uncoupling protein 1 * futile fatty acid cycle
OECD category: Physiology (including cytology)
Impact factor: 5.8, year: 2022
Method of publishing: Open access
https://doi.org/10.1016/j.bcp.2024.116042

Fibroblast growth factor 21 (FGF21) reduces body weight, which was attributed to induced energy expenditure (EE). Conflicting data have been published on the role of uncoupling protein 1 (UCP1) in this effect. Therefore, we aimed to revisit the thermoregulatory effects of FGF21 and their implications for body weight regulation. We found that an 8day treatment with FGF21 lowers body weight to similar extent in both wildtype (WT) and UCP1-deficient (KO) mice fed highfat diet. In WT mice, this effect is solely due to increased EE, associated with a strong activation of UCP1 and with excess heat dissipated through the tail. This thermogenesis takes place in the interscapular region and can be attenuated by a beta-adrenergic inhibitor propranolol. In KO mice, FGF21-induced weight loss correlates with a modest increase in EE, which is independent of adrenergic signaling, and with a reduced energy intake. Interestingly, the gene expression profile of interscapular brown adipose tissue (but not subcutaneous white adipose tissue) of KO mice is massively affected by FGF21, as shown by increased expression of genes encoding triacylglycerol/free fatty acid cycle enzymes. Thus, FGF21 elicits central thermogenic and pyretic effects followed by a concomitant increase in EE and body temperature, respectively. The associated weight loss is strongly dependent on UCP1-based thermogenesis. However, in the absence of UCP1, alternative mechanisms of energy dissipation may contribute, possibly based on futile triacylglycerol/free fatty acid cycling in brown adipose tissue and reduced food intake.
Permanent Link: https://hdl.handle.net/11104/0352537