文章基本信息

标题：Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue
本地全文：下载
作者：Souza, Sandra C. ; Christoffolete, Marcelo A. ; Ribeiro, Miriam O. 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2007
卷号：48
期号：6
页码：1273-1279
DOI：10.1194/jlr.M700047-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：In response to cold, norepinephrine (NE)-induced triacylglycerolhydrolysis (lipolysis) in adipocytes of brown adipose tissue(BAT) provides fatty acid substrates to mitochondria for heatgeneration (adaptive thermogenesis). NE-induced lipolysis ismediated by protein kinase A (PKA)-dependent phosphorylationof perilipin, a lipid droplet-associated protein that is themajor regulator of lipolysis. We investigated the role of perilipinPKA phosphorylation in BAT NE-stimulated thermogenesis usinga novel mouse model in which a mutant form of perilipin, lackingall six PKA phosphorylation sites, is expressed in adipocytesof perilipin knockout (Peri KO) mice. Here, we show that despitea normal mitochondrial respiratory capacity, NE-induced lipolysisis abrogated in the interscapular brown adipose tissue (IBAT)of these mice. This lipolytic constraint is accompanied by adramatic blunting ( $~$ 70%) of the in vivo thermal response to NE.Thus, in the presence of perilipin, PKA-mediated perilipin phosphorylationis essential for NE-dependent lipolysis and full adaptive thermogenesisin BAT. In IBAT of Peri KO mice, increased basal lipolysis attributableto the absence of perilipin is sufficient to support a rapidNE-stimulated temperature increase ( $~$ 3.0°C) comparable tothat in wild-type mice. This observation suggests that one ormore NE-dependent mechanism downstream of perilipin phosphorylationis required to initiate and/or sustain the IBAT thermal response. Supplementary key words norepinephrine-induced thermal response • protein kinase A-stimulated lipolysis • brown adipocytes Abbreviations: ATGL, adipose tissue triacylglycerol lipase; BAT, brown adipose tissue; HSL, hormone-sensitive lipase; IBAT, interscapular brown adipose tissue; NE, norepinephrine; Peri A, perilipin isoform A; Peri KO, perilipin knockout; PKA, protein kinase A; TAG, triacylglycerol; UCP1, uncoupling protein-1; WAT, white adipose tissue; WT, wild-type