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Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue

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タイトル: Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue
著者: Souza, Sandra C. 著作を一覧する
Christoffolete, Marcelo A. 著作を一覧する
Ribeiro, Miriam O. 著作を一覧する
Miyoshi, Hideaki 著作を一覧する
Strissel, Katherine J. 著作を一覧する
Stancheva, Zlatina S. 著作を一覧する
Rogers, Nicole H. 著作を一覧する
D'Eon, Tara M. 著作を一覧する
Perfield, James W., II 著作を一覧する
Imachi, Hitomi 著作を一覧する
Obin, Martin S. 著作を一覧する
Bianco, Antonio C. 著作を一覧する
Greenberg, Andrew S. 著作を一覧する
キーワード: norepinephrine-induced thermal response
protein kinase A-stimulated lipolysis
brown adipocytes
発行日: 2007年 6月
出版者: American Society for Biochemistry and Molecular Biology
誌名: Journal of lipid research
巻: 48
号: 6
開始ページ: 1273
終了ページ: 1279
出版社 DOI: 10.1194/jlr.M700047-JLR200
抄録: In response to cold, norepinephrine (NE)-induced triacylglycerol hydrolysis (lipolysis) in adipocytes of brown adipose tissue (BAT) provides fatty acid substrates to mitochondria for heat generation (adaptive thermogenesis). NE-induced lipolysis is mediated by protein kinase A (PKA)-dependent phosphorylation of perilipin, a lipid droplet-associated protein that is the major regulator of lipolysis. We investigated the role of perilipin PKA phosphorylation in BAT NE-stimulated thermogenesis using a novel mouse model in which a mutant form of perilipin, lacking all six PKA phosphorylation sites, is expressed in adipocytes of perilipin knockout (Peri KO) mice. Here, we show that despite a normal mitochondrial respiratory capacity, NE-induced lipolysis is abrogated in the interscapular brown adipose tissue (IBAT) of these mice. This lipolytic constraint is accompanied by a dramatic blunting (∼70%) of the in vivo thermal response to NE. Thus, in the presence of perilipin, PKA-mediated perilipin phosphorylation is essential for NE-dependent lipolysis and full adaptive thermogenesis in BAT. In IBAT of Peri KO mice, increased basal lipolysis attributable to the absence of perilipin is sufficient to support a rapid NE-stimulated temperature increase (∼3.0°C) comparable to that in wild-type mice. This observation suggests that one or more NE-dependent mechanism downstream of perilipin phosphorylation is required to initiate and/or sustain the IBAT thermal response.
Rights: This research was originally published in Journal of Lipid Research. Souza, S. C., M. A. Christoffolete, M. O. Ribeiro, H. Miyoshi, K. J. Strissel, Z. S. Stancheva, N. H. Rogers, T. M. D'Eon, J. W. Perfield, II, H. Imachi, M. S. Obin, A. C. Bianco, and A. S. Greenberg. Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue. J. Lipid Res. 2007; 48:1273–1279. © the American Society for Biochemistry and Molecular Biology.
資料タイプ: article
URI: http://hdl.handle.net/2115/67272
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 三好 秀明

 

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