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
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
U2 - 10.1016/j.cmet.2017.07.016
DO - 10.1016/j.cmet.2017.07.016
M3 - Article
AN - SCOPUS:85025819294
SN - 1550-4131
VL - 26
SP - 437-446.e5
JO - Cell Metabolism
JF - Cell Metabolism
IS - 2
ER -