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A pyrexic effect of FGF21 independent of energy expenditure and UCP1
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SYSNO ASEP 0546860 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title A pyrexic effect of FGF21 independent of energy expenditure and UCP1 Author(s) Zouhar, Petr (FGU-C) RID, ORCID, SAI
Janovská, Petra (FGU-C) RID, ORCID
Stanić, Sara (FGU-C)
Bardová, Kristina (FGU-C) RID, ORCID, SAI
Funda, Jiří (FGU-C) ORCID
Haberlová, Blanka (FGU-C)
Andersen, B. (DK)
Rossmeisl, Martin (FGU-C) RID, ORCID
Cannon, B. (SE)
Kopecký, Jan (FGU-C) RID, ORCID
Nedergaard, J. (SE)Article number 101324 Source Title Molecular Metabolism. - : Elsevier - ISSN 2212-8778
Roč. 53, Nov (2021)Number of pages 16 s. Language eng - English Country NL - Netherlands Keywords UCP1 ; thermoneutrality ; beiging/browning ; obesity ; body temperature control Subject RIV ED - Physiology OECD category Physiology (including cytology) R&D Projects GJ19-05356Y GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000702820300003 EID SCOPUS 85114918151 DOI 10.1016/j.molmet.2021.101324 Annotation Objective: Administration of FGF21 to mice reduces body weight and increases body temperature. The increase in body temperature is generally interpreted as hyperthermia, i.e. a condition secondary to the increase in energy expenditure (heat production). Here, we examine an alternative hypothesis: that FGF21 has a direct pyrexic effect, i.e. FGF21 increases body temperature independently of any effect on energy expenditure. Methods: We studied the effects of FGF21 treatment on body temperature and energy expenditure in high-fat-diet-fed and chow-fed mice exposed acutely to various ambient temperatures, in high-fat diet-fed mice housed at 30 °C (i.e. at thermoneutrality), and in mice lacking uncoupling protein 1 (UCP1). Results: In every model studied, FGF21 increased body temperature, but energy expenditure was increased only in some models. The effect of FGF21 on body temperature was more (not less, as expected in hyperthermia) pronounced at lower ambient temperatures. Effects on body temperature and energy expenditure were temporally distinct (daytime versus nighttime). FGF21 enhanced UCP1 protein content in brown adipose tissue (BAT), there was no measurable UCP1 protein in inguinal brite/beige adipose tissue. FGF21 increased energy expenditure through adrenergic stimulation of BAT. In mice lacking UCP1, FGF21 did not increase energy expenditure but increased body temperature by reducing heat loss, e.g. a reduced tail surface temperature. Conclusion: The effect of FGF21 on body temperature is independent of UCP1 and can be achieved in the absence of any change in energy expenditure. Since elevated body temperature is a primary effect of FGF21 and can be achieved without increasing energy expenditure, only limited body weight-lowering effects of FGF21 may be expected. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2022 Electronic address https://doi.org/10.1016/j.molmet.2021.101324
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