TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis.

Journal Article (Journal Article)

PGC1α is a key transcriptional coregulator of oxidative metabolism and thermogenesis. Through a high-throughput chemical screen, we found that molecules antagonizing the TRPVs (transient receptor potential vanilloid), a family of ion channels, induced PGC1α expression in adipocytes. In particular, TRPV4 negatively regulated the expression of PGC1α, UCP1, and cellular respiration. Additionally, it potently controlled the expression of multiple proinflammatory genes involved in the development of insulin resistance. Mice with a null mutation for TRPV4 or wild-type mice treated with a TRPV4 antagonist showed elevated thermogenesis in adipose tissues and were protected from diet-induced obesity, adipose inflammation, and insulin resistance. This role of TRPV4 as a cell-autonomous mediator for both the thermogenic and proinflammatory programs in adipocytes could offer a target for treating obesity and related metabolic diseases.

Full Text

Duke Authors

Cited Authors

  • Ye, L; Kleiner, S; Wu, J; Sah, R; Gupta, RK; Banks, AS; Cohen, P; Khandekar, MJ; Boström, P; Mepani, RJ; Laznik, D; Kamenecka, TM; Song, X; Liedtke, W; Mootha, VK; Puigserver, P; Griffin, PR; Clapham, DE; Spiegelman, BM

Published Date

  • September 28, 2012

Published In

Volume / Issue

  • 151 / 1

Start / End Page

  • 96 - 110

PubMed ID

  • 23021218

Pubmed Central ID

  • PMC3477522

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2012.08.034


  • eng

Conference Location

  • United States