title: Lack of TRPV2 impairs thermogenesis in mouse brown adipose tissue.
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.
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Okazaki, Japan Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan.
authors.forename: Wuping
authors.initials: W
authors.lastname: Sun
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Okazaki, Japan Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan kuchida@nips.ac.jp tominaga@nips.ac.jp.
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Okazaki, Japan Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Okazaki, Japan.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture Kyoto University, Uji, Japan.
authors.forename: Minji
authors.initials: M
authors.lastname: Kim
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Okazaki, Japan Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Takayama
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture Kyoto University, Uji, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture Kyoto University, Uji, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Molecular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Wakabayashi
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture Kyoto University, Uji, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
authors.affiliation: Department of Molecular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Okazaki, Japan Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan kuchida@nips.ac.jp tominaga@nips.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D022722:Thermogenesis
chemical_list: D015220:Calcium Channels; D011943:Receptors, Adrenergic, beta; D050916:TRPV Cation Channels; C485717:Trpv2 protein, mouse; D002118:Calcium
keywords: BAT; Ca2+; TRPV2; UCP1; thermogenesis