Details
| Original language | English |
|---|---|
| Pages (from-to) | 437-446 |
| Journal | Cell metabolism |
| Volume | 26 |
| Issue number | 2 |
| Publication status | Published - 1 Aug 2017 |
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.
Keywords
- adaptive thermogenesis, beige adipose tissue, browning, cold exposure, endocrine cross talk, energy metabolism, mitochondrial respiration, Pm20d1, uncoupling protein
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Physiology
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology
Sustainable Development Goals
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In: Cell metabolism, Vol. 26, No. 2, 01.08.2017, p. 437-446.
Research output: Contribution to journal › Article › Research › peer review
}
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 -