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Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue

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Title: Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue
Authors: Souza, Sandra C. Browse this author
Christoffolete, Marcelo A. Browse this author
Ribeiro, Miriam O. Browse this author
Miyoshi, Hideaki Browse this author →KAKEN DB
Strissel, Katherine J. Browse this author
Stancheva, Zlatina S. Browse this author
Rogers, Nicole H. Browse this author
D'Eon, Tara M. Browse this author
Perfield, James W., II Browse this author
Imachi, Hitomi Browse this author
Obin, Martin S. Browse this author
Bianco, Antonio C. Browse this author
Greenberg, Andrew S. Browse this author
Keywords: norepinephrine-induced thermal response
protein kinase A-stimulated lipolysis
brown adipocytes
Issue Date: Jun-2007
Publisher: American Society for Biochemistry and Molecular Biology
Journal Title: Journal of lipid research
Volume: 48
Issue: 6
Start Page: 1273
End Page: 1279
Publisher DOI: 10.1194/jlr.M700047-JLR200
Abstract: 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.
Type: article
URI: http://hdl.handle.net/2115/67272
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 三好 秀明

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