TY - JOUR

T1 - Long-Term Cold Adaptation Does Not Require FGF21 or UCP1

AU - Keipert, Susanne

AU - Kutschke, Maria

AU - Ost, Mario

AU - Schwarzmayr, Thomas

AU - van Schothorst, Evert M.

AU - Lamp, Daniel

AU - Brachthäuser, Laura

AU - Hamp, Isabel

AU - Mazibuko, Sithandiwe E.

AU - Hartwig, Sonja

AU - Lehr, Stefan

AU - Graf, Elisabeth

AU - Plettenburg, Oliver

AU - Neff, Frauke

AU - Tschöp, Matthias H.

AU - Jastroch, Martin

N1 - Funding Information: We thank Sandy Lösecke for excellent technical assistance. This work was supported by a grant to S.K. and S.H. from the German Center for Diabetes Research (DZD) and supported in part by funding to M.H.T. from the Alexander von Humboldt Foundation, the Helmholtz Alliance ICEMED and the Helmholtz Initiative on Personalized Medicine iMed by Helmholtz Association, and the Helmholtz cross-program topic “Metabolic Dysfunction.” The Graphical Abstract was created using Servier Medical Art (http://www.servier.com). Publisher Copyright: © 2017 Elsevier Inc.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - 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.

AB - 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.

KW - adaptive thermogenesis

KW - beige adipose tissue

KW - browning

KW - cold exposure

KW - endocrine cross talk

KW - energy metabolism

KW - mitochondrial respiration

KW - Pm20d1

KW - uncoupling protein

UR - http://www.scopus.com/inward/record.url?scp=85025819294&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2017.07.016

DO - 10.1016/j.cmet.2017.07.016

M3 - Article

C2 - 28768181

AN - SCOPUS:85025819294

VL - 26

SP - 437

EP - 446

JO - Cell metabolism

JF - Cell metabolism

SN - 1550-4131

IS - 2

ER -