Lack of TRPV2 impairs thermogenesis in mouse brown adipose tissue. (11th February 2016)

• Record Type: Journal Article
• Authors: Sun, Wuping; Uchida, Kunitoshi; Suzuki, Yoshiro; Zhou, Yiming; Kim, Minji; Takayama, Yasunori; Takahashi, Nobuyuki; Goto, Tsuyoshi; Wakabayashi, Shigeo; Kawada, Teruo; Iwata, Yuko; Tominaga, Makoto
• Is Part Of: EMBO reports. Volume 17:Number 3(2016:Mar.)
• Page Start: 383
• Page End: 399
• Publication Date: 2016-02-11
• Subjects: BAT -- Ca2+ -- thermogenesis -- TRPV2 -- UCP1; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201540819
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: Brown adipose tissue (BAT), a major site for mammalian non‐shivering thermogenesis, could be a target for prevention and treatment of human obesity. Transient receptor potential vanilloid 2 (TRPV2), a Ca 2+ ‐permeable non‐selective cation channel, plays vital roles in the regulation of various cellular functions. Here, we show that TRPV2 is expressed in brown adipocytes and that mRNA levels of thermogenic genes are reduced in both cultured brown adipocytes and BAT from TRPV2 knockout (TRPV2KO) mice. The induction of thermogenic genes in response to β‐adrenergic receptor stimulation is also decreased in TRPV2KO brown adipocytes and suppressed by reduced intracellular Ca 2+ concentrations in wild‐type brown adipocytes. In addition, TRPV2KO mice have more white adipose tissue and larger brown adipocytes and show cold intolerance, and lower BAT temperature increases in response to β‐adrenergic receptor stimulation. Furthermore, TRPV2KO mice have increased body weight and fat upon high‐fat‐diet treatment. Based on these findings, we conclude that TRPV2 has a role in BAT thermogenesis and could be a target for human obesity therapy. Synopsis: Mice lacking TRPV2 show impaired BAT thermogenesis and are prone to obesity on a high‐fat diet. TRPV2‐mediated increases in thermogenic gene expression upon β‐adrenergic receptor stimulation might involve intracellular calcium signals. TRPV2KO mice show cold intolerance and impaired BAT thermogenesis upon β‐adrenergic receptor activation. TRPV2KO mice are prone to be obese and insulin resistant on a high‐fat diet. TRPV2‐mediated increases in intracellular calcium concentrations might promote thermogenic gene expression upon β‐adrenergic receptor activation. Abstract : Mice lacking TRPV2 show impaired BAT thermogenesis and are prone to obesity on a high fat diet. TRPV2‐mediated increases in thermogenic gene expression upon β‐adrenergic receptor stimulation might involve intracellular calcium signals.