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Keipert, S. ; Kutschke, M. ; Ost, M.* ; Schwarzmayr, T. ; van Schothorst, E.M.* ; Lamp, D. ; Brachthäuser, L. ; Hamp, I. ; Mazibuko-Mbeje, S. ; Hartwig, S.* ; Lehr, S.* ; Graf, E. ; Plettenburg, O. ; Neff, F. ; Tschöp, M.H. ; Jastroch, M.

Long-term cold adaptation does not require FGF21 or UCP1.

Cell Metab. 26, 437-446.e5 (2017)
Verlagsversion DOI PMC
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Brown adipose tissue (BAT)-dependent thermogenesis and its suggested augmenting hormone, FGF21, are potential therapeutic targets in current obesity and diabetes research. Here, we studied the role of UCP1 and FGF21 for metabolic homeostasis in the cold and dissected underlying molecular mechanisms using UCP1-FGF21 double-knockout mice. We report that neither UCP1 nor FGF21, nor even compensatory increases of FGF21 serum levels in UCP1 knockout mice, are required for defense of body temperature or for maintenance of energy metabolism and body weight. Remarkably, cold-induced browning of inguinal white adipose tissue (iWAT) is FGF21 independent. Global RNA sequencing reveals major changes in response to UCP1- but not FGF21-ablation in BAT, iWAT, and muscle. Markers of mitochondrial failure and inflammation are observed in BAT, but in particular the enhanced metabolic reprogramming in iWAT supports the thermogenic role of UCP1 and excludes an important thermogenic role of endogenous FGF21 in normal cold acclimation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Adaptive Thermogenesis ; Beige Adipose Tissue ; Browning ; Cold Exposure ; Endocrine Cross Talk ; Energy Metabolism ; Mitochondrial Respiration ; Pm20d1 ; Uncoupling Protein
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Zeitschrift Cell Metabolism
Quellenangaben Band: 26, Heft: 2, Seiten: 437-446.e5 Artikelnummer: , Supplement: ,
Verlag Elsevier
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Institute of Human Genetics (IHG)
Institute of Medicinal Chemistry (IMC)