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Prolonged FGF21 treatment increases energy expenditure and induces weight loss in obese mice independently of UCP1 and adrenergic signaling
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SYSNO ASEP 0584426 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Prolonged FGF21 treatment increases energy expenditure and induces weight loss in obese mice independently of UCP1 and adrenergic signaling Author(s) Stanić, Sara (FGU-C)
Bardová, Kristina (FGU-C) RID, ORCID, SAI
Janovská, Petra (FGU-C) RID, ORCID
Rossmeisl, Martin (FGU-C) RID, ORCID
Kopecký, Jan (FGU-C) RID, ORCID
Zouhar, Petr (FGU-C) RID, ORCID, SAIArticle number 116042 Source Title Biochemical Pharmacology. - : Elsevier - ISSN 0006-2952
Roč. 221, March (2024)Number of pages 12 s. Language eng - English Country GB - United Kingdom Keywords fibroblast growth factor 21 ; energy expenditure ; weight loss ; brown adipose tissue ; uncoupling protein 1 ; futile fatty acid cycle OECD category Physiology (including cytology) R&D Projects GJ19-05356Y GA ČR - Czech Science Foundation (CSF) LX22NPO5104 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 001181376000001 EID SCOPUS 85184864240 DOI 10.1016/j.bcp.2024.116042 Annotation 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. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2025 Electronic address https://doi.org/10.1016/j.bcp.2024.116042
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