TRPV4 Is a Regulator of Adipose Oxidative Metabolism, Inflammation, and Energy Homeostasis

被引：274

作者：

Ye, Li ^{[1
,2
]}

Kleiner, Sandra ^{[1
,2
]}

Wu, Jun ^{[1
,2
]}

Sah, Rajan ^{[3
,4
]}

Gupta, Rana K. ^{[1
,2
]}

Banks, Alexander S. ^{[1
,2
]}

Cohen, Paul ^{[1
,2
]}

Khandekar, Melin J. ^{[1
,2
]}

Bostroem, Pontus ^{[1
,2
]}

Mepani, Rina J. ^{[1
,2
]}

Laznik, Dina ^{[1
,2
]}

Kamenecka, Theodore M. ^{[5
]}

Song, Xinyi ^{[5
]}

Liedtke, Wolfgang ^{[6
]}

Mootha, Vamsi K. ^{[7
,8
]}

Puigserver, Pere ^{[1
,2
]}

Griffin, Patrick R. ^{[5
]}

Clapham, David E. ^{[3
,4
]}

Spiegelman, Bruce M. ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Cardiol,Boston Childrens Hosp, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[5] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA

[6] Duke Univ, Dept Med, Med Ctr, Durham, NC 27710 USA

[7] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA

[8] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

来源：

CELL | 2012年 / 151卷 / 01期

关键词：

DIET-INDUCED OBESITY; WHITE FAT DEPOTS; BROWN ADIPOCYTES; INSULIN-RESISTANCE; CATION CHANNEL; GENE-EXPRESSION; PROTEIN-KINASE; TISSUE; ACTIVATION; MICE;

D O I：

10.1016/j.cell.2012.08.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

PGC1 alpha 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 PGC1 alpha expression in adipocytes. In particular, TRPV4 negatively regulated the expression of PGC1 alpha, 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.

引用

页码：96 / 110

页数：15

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