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

Susanne Keipert1, Maria Kutschke2, Mario Ost3

  • 1Institute for Diabetes and Obesity, Helmholtz Diabetes Center, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.

Cell Metabolism
|August 3, 2017
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Summary
This summary is machine-generated.

Neither UCP1 nor FGF21 are essential for cold-induced thermogenesis or metabolic homeostasis. This research on knockout mice reveals UCP1

Keywords:
Pm20d1adaptive thermogenesisbeige adipose tissuebrowningcold exposureendocrine cross talkenergy metabolismmitochondrial respirationuncoupling protein

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Area of Science:

  • Metabolic research
  • Obesity and diabetes research
  • Thermogenesis mechanisms

Background:

  • Brown adipose tissue (BAT) thermogenesis and FGF21 are potential therapeutic targets for obesity and diabetes.
  • Understanding the roles of UCP1 and FGF21 in metabolic homeostasis during cold exposure is crucial.

Purpose of the Study:

  • To investigate the roles of UCP1 and FGF21 in metabolic homeostasis during cold exposure.
  • To dissect the molecular mechanisms underlying thermogenesis using UCP1-FGF21 double-knockout mice.

Main Methods:

  • Utilized UCP1-FGF21 double-knockout mice to study metabolic homeostasis in the cold.
  • Performed global RNA sequencing on BAT, iWAT, and muscle tissues.
  • Analyzed body temperature, energy metabolism, and body weight regulation.

Main Results:

  • Neither UCP1 nor FGF21 are required for defending body temperature or maintaining energy metabolism and body weight.
  • Cold-induced browning of inguinal white adipose tissue (iWAT) is independent of FGF21.
  • UCP1-ablation, but not FGF21-ablation, caused significant changes in gene expression in BAT, iWAT, and muscle, including markers of mitochondrial dysfunction and inflammation in BAT.

Conclusions:

  • UCP1 plays a significant role in cold acclimation and metabolic reprogramming in iWAT.
  • Endogenous FGF21 does not appear to have a major thermogenic role in normal cold acclimation.
  • The findings challenge the necessity of UCP1 and FGF21 for basic thermoregulation and metabolic balance in the cold.