Stress turns on the heat: Regulation of mitochondrial biogenesis and UCP1 by ROS in adipocytes

Adipocyte. 2017 Jan 2;6(1):56-61. doi: 10.1080/21623945.2016.1273298. Epub 2016 Dec 16.


Reactive oxygen species (ROS) production and oxidative stress (OS) in adipose tissue are associated with obesity and insulin resistance (IR). The nature of this relationship i.e., cause and effect or consequence has not been clearly determined. We provide evidence that elevated mitochondrial ROS generated by adipocytes from mice with diet-induced obesity (DIO) represents an adaptive mechanism that precipitates fatty acid oxidation, mitochondrial biogenesis, and mitochondrial uncoupling in an effort to defend against weight gain. Consistent with that, mice with adipocyte-specific deletion of manganese superoxide dismutase (MnSOD) exhibit increased adipocyte superoxide generation and are protected from weight gain and insulin resistance which otherwise develops in wild-type (WT) mice that consume an obesogenic diet. The defense mechanism displayed by MnSOD-deficiency in fat cells appears to be mediated by a dual effect of ROS on inefficient substrate oxidation through uncoupling of oxidative phosphorylation and enhanced mitochondrial biogenesis. The aim of this commentary is to summarize and contextualize additional evidence supporting the importance of mitochondrial ROS in the regulation of mitochondrial biogenesis and the modulation of uncoupling protein 1 (UCP1) expression and activation in both white and brown adipocytes.

Keywords: MnSOD; ROS; Uncoupling protein 1 (UCP1); brown adipose tissue; mitochondria; oxidative modification; proton leak; superoxide.

Publication types

  • Review

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Animals
  • Energy Metabolism / drug effects
  • Mice
  • Mitochondria / drug effects
  • Mitochondrial Proteins / metabolism
  • Organelle Biogenesis
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism*
  • Superoxide Dismutase / deficiency
  • Superoxide Dismutase / metabolism*
  • Uncoupling Protein 1 / metabolism*


  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Uncoupling Protein 1
  • Superoxide Dismutase