Activation of TRPV2 negatively regulates the differentiation of mouse brown adipocytes.
Transient receptor potential vanilloid 2 (TRPV2) acts as a Ca(2+)-permeable non-selective cation channel that has been reported to be sensitive to temperature, mechanical force, and some chemicals. We recently showed that TRPV2 is critical for maintenance of the thermogenic function of brown adipose tissue in mice. However, the involvement of TRPV2 in the differentiation of brown adipocytes remains unexplored. We found that the expression of TRPV2 was dramatically increased during the differentiation of brown adipocytes. Non-selective TRPV2 agonists (2-aminoethoxydiphenyl borate and lysophosphatidylcholine) inhibited the differentiation of brown adipocytes in a dose-dependent manner during the early stage of differentiation of brown adipocytes. The inhibition was rescued by a TRPV2-selective antagonist, SKF96365 (SKF). Mechanical force, which activates TRPV2, also inhibited the differentiation of brown adipocytes in a strength-dependent manner, and the effect was reversed by SKF. In addition, the inhibition of adipocyte differentiation by either TRPV2 ligand or mechanical stimulation was significantly smaller in the cells from TRPV2KO mice. Moreover, calcineurin inhibitors, cyclosporine A and FK506, partially reversed TRPV2 activation-induced inhibition of brown adipocyte differentiation. Thus, we conclude that TRPV2 might be involved in the modulation of brown adipocyte differentiation partially via a calcineurin pathway.
Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi, 444-8787, Japan.|Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan.
Wuping
W
Sun
Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi, 444-8787, Japan. kuchida@nips.ac.jp.|Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan. kuchida@nips.ac.jp.
Kunitoshi
K
Uchida
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Nobuyuki
N
Takahashi
Department of Molecular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Yuko
Y
Iwata
Department of Molecular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Shigeo
S
Wakabayashi
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Tsuyoshi
T
Goto
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Teruo
T
Kawada
Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi, 444-8787, Japan. tominaga@nips.ac.jp.|Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan. tominaga@nips.ac.jp.
Makoto
M
Tominaga
D052437:Adipocytes, Brown / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D065095:Calcineurin Inhibitors / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology
D001896:Boron Compounds; D065095:Calcineurin Inhibitors; D015220:Calcium Channels; D007093:Imidazoles; D008244:Lysophosphatidylcholines; D050916:TRPV Cation Channels; C485717:Trpv2 protein, mouse; D016572:Cyclosporine; C109986:2-aminoethoxydiphenyl borate; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D016559:Tacrolimus
Adipocyte; Ca2+; Calcineurin; Differentiation; Mechanical force (membrane stretch); Obesity; Transient receptor potential channels (TRP channels)