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Keipert, S. ; Lutter, D. ; Schroeder, B.O.* ; Brandt, D. ; Ståhlman, M.* ; Schwarzmayr, T. ; Graf, E. ; Fuchs, H. ; Hrabě de Angelis, M. ; Tschöp, M.H. ; Rozman, J. ; Jastroch, M.

Endogenous FGF21-signaling controls paradoxical obesity resistance of UCP1-deficient mice.

Nat. Commun. 11:624 (2020)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Brown adipose thermogenesis increases energy expenditure and relies on uncoupling protein 1 (UCP1), however, UCP1 knock-out mice show resistance to diet-induced obesity at room temperature. Here, the authors show that this resistance relies on FGF21-signaling, inducing the browning of white adipose tissue.Uncoupling protein 1 (UCP1) executes thermogenesis in brown adipose tissue, which is a major focus of human obesity research. Although the UCP1-knockout (UCP1 KO) mouse represents the most frequently applied animal model to judge the anti-obesity effects of UCP1, the assessment is confounded by unknown anti-obesity factors causing paradoxical obesity resistance below thermoneutral temperatures. Here we identify the enigmatic factor as endogenous FGF21, which is primarily mediating obesity resistance. The generation of UCP1/FGF21 double-knockout mice (dKO) fully reverses obesity resistance. Within mild differences in energy metabolism, urine metabolomics uncover increased secretion of acyl-carnitines in UCP1 KOs, suggesting metabolic reprogramming. Strikingly, transcriptomics of metabolically important organs reveal enhanced lipid and oxidative metabolism in specifically white adipose tissue that is fully reversed in dKO mice. Collectively, this study characterizes the effects of endogenous FGF21 that acts as master regulator to protect from diet-induced obesity in the absence of UCP1.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Brown Adipose-tissue; Diet-induced Thermogenesis; Energy-expenditure; Cold-exposure; Bile-acids; Fgf21; White; Fat; Balance; Ucp1
Sprache
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 11, Heft: 1, Seiten: , Artikelnummer: 624 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Institute of Human Genetics (IHG)
Institute of Experimental Genetics (IEG)
POF Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Helmholtz Diabetes Center
Genetics and Epidemiology
PSP-Element(e) G-501900-221
G-502200-001
G-500700-001
G-500600-001
G-500692-001
DOI 10.1038/s41467-019-14069-2
WOS ID WOS:000513245600012
Scopus ID 85078835151
PubMed ID 32005798
Erfassungsdatum 2020-02-03
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