Long-Term Cold Adaptation Does Not Require FGF21 or UCP1

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

doi:10.1016/j.cmet.2017.07.016

Long-Term Cold Adaptation Does Not Require FGF21 or UCP1

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

110 Citations (Scopus)

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.

Original language	English
Pages (from-to)	437-446.e5
Journal	Cell Metabolism
Volume	26
Issue number	2
DOIs	https://doi.org/10.1016/j.cmet.2017.07.016
Publication status	Published - 1 Aug 2017

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

adaptive thermogenesis
beige adipose tissue
browning
cold exposure
endocrine cross talk
energy metabolism
mitochondrial respiration
Pm20d1
uncoupling protein

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title = "Long-Term Cold Adaptation Does Not Require FGF21 or UCP1",

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.",

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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

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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 -

Long-Term Cold Adaptation Does Not Require FGF21 or UCP1

Abstract

UN SDGs

Keywords

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