Long-Term Cold Adaptation Does Not Require FGF21 or UCP1

authored by: Susanne Keipert, Maria Kutschke, Mario Ost, Thomas Schwarzmayr, Evert M. van Schothorst, Daniel Lamp, Laura Brachthäuser, Isabel Hamp, Sithandiwe E. Mazibuko, Sonja Hartwig, Stefan Lehr, Elisabeth Graf, Oliver Plettenburg, Frauke Neff, Matthias H. Tschöp, Martin Jastroch
Abstract: 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.
Organisation(s): Institute of Organic Chemistry
External Organisation(s): Helmholtz Zentrum München - German Research Center for Environmental Health
German Center for Diabetes Research (DZD)
German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)
Wageningen University and Research
Technical University of Munich (TUM)
Philipps-Universität Marburg
German Diabetes Center (DDZ)
Type: Article
Journal: Cell metabolism
Volume: 26
Pages: 437-446
ISSN: 1550-4131
Publication date: 01.08.2017
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Physiology, Molecular Biology, Cell Biology
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): https://doi.org/10.1016/j.cmet.2017.07.016 (Access: Open)