TRPC1 regulates brown adipose tissue activity in a PPARγ-dependent manner

Am J Physiol Endocrinol Metab. 2018 Nov 1;315(5):E825-E832. doi: 10.1152/ajpendo.00170.2017. Epub 2018 Jul 10.

Abstract

Brown adipose tissue (BAT) has the unique ability to convert energy stored in the form of triglycerides into heat. This property makes BAT a target tissue to increase energy expenditure and improve systemic metabolic control. TRPC1 is a founding member of the TRP protein family that also includes several temperature sensitive channels. We show that TRPC1 is highly expressed in all adipocyte depots including BAT and that Trpc1-deficient mice are prone to weight gain and manifest reduced metabolic control. We also demonstrate that knockdown of TRPC1 in cultured brown adipocytes leads to a downregulation of several metabolic genes, including UCP1 and PPARγ, as well as upregulation of a BAT-specific thermosensitive channel TRPV2, ultimately resulting in impaired respiratory function. We also show that TRPC1 is a possible target of PPARγ, suggesting that TRPC1 is a downstream component of a mechanism that translates metabolic or environmental stimuli into output in the form of BAT activity. Better understanding of the possible role of TRPC1 and other TRP channels in body temperature regulation and BAT function may help us to develop obesity therapies based on BAT activation.

Keywords: brown adipose tissue; peroxisome proliferator‐activated receptor-γ; transient receptor protein channel 1; uncoupling protein 1.

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Down-Regulation
  • Energy Metabolism / genetics*
  • Mice
  • Mice, Knockout
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism
  • Up-Regulation
  • Weight Gain / genetics*

Substances

  • Calcium Channels
  • PPAR gamma
  • TRPC Cation Channels
  • TRPV Cation Channels
  • Trpv2 protein, mouse
  • Uncoupling Protein 1
  • transient receptor potential cation channel, subfamily C, member 1