Cardiac-specific overexpression of perilipin 5 provokes severe cardiac steatosis via the formation of a lipolytic barrier

被引：107

作者：

Pollak, Nina M. ^{[1
]}

Schweiger, Martina ^{[1
]}

Jaeger, Doris ^{[1
]}

Kolb, Dagmar ^{[2
]}

Kumari, Manju ^{[1
]}

Schreiber, Renate ^{[1
]}

Kolleritsch, Stephanie ^{[1
]}

Markolin, Philipp ^{[1
]}

Grabner, Gernot F. ^{[1
]}

Heier, Christoph ^{[1
]}

Zierler, Kathrin A. ^{[1
]}

Ruelicke, Thomas ^{[3
,4
]}

Zimmermann, Robert ^{[1
]}

Lass, Achim ^{[1
]}

Zechner, Rudolf ^{[1
]}

Haemmerle, Guenter ^{[1
]}

机构：

[1] Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

[2] Med Univ Graz, Med Res Ctr, A-8036 Graz, Austria

[3] Biomodels Austria, A-1210 Vienna, Austria

[4] Univ Vet Med, Inst Lab Anim Sci, A-1210 Vienna, Austria

来源：

JOURNAL OF LIPID RESEARCH | 2013年 / 54卷 / 04期

基金：

奥地利科学基金会;

关键词：

adipose triglyceride lipase; cardiac lipid; energy metabolism; LIPID DROPLET SYNTHESIS; FATTY-ACID; STORAGE DISEASE; PAT FAMILY; PROTEIN; METABOLISM; CATABOLISM; TISSUE; HEART; CGI-58;

D O I：

10.1194/jlr.M034710

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cardiac triacylglycerol (TG) catabolism critically depends on the TG hydrolytic activity of adipose triglyceride lipase (ATGL). Perilipin 5 (Plin5) is expressed in cardiac muscle (CM) and has been shown to interact with ATGL and its coactivator comparative gene identification-58 (CGI-58). Furthermore, ectopic Plin5 expression increases cellular TG content and Plin5-deficient mice exhibit reduced cardiac TG levels. In this study we show that mice with cardiac muscle-specific overexpression of perilipin 5 (CM-Plin5) massively accumulate TG in CM, which is accompanied by moderately reduced fatty acid (FA) oxidizing gene expression levels. Cardiac lipid droplet (LD) preparations from CM of CM-Plin5 mice showed reduced ATGL- and hormone-sensitive lipase-mediated TG mobilization implying that Plin5 overexpression restricts cardiac lipolysis via the formation of a lipolytic barrier. To test this hypothesis, we analyzed TG hydrolytic activities in preparations of Plin5-, ATGL-, and CGI-58-transfected cells. In vitro ATGL-mediated TG hydrolysis of an artificial micellar TG substrate was not inhibited by the presence of Plin5, whereas Plin5-coated LDs were resistant toward ATGL-mediated TG catabolism. These findings strongly suggest that Plin5 functions as a lipolytic barrier to protect the cardiac TG pool from uncontrolled TG mobilization and the excessive release of free FAs.-Pollak, N. M., M. Schweiger, D. Jaeger, D. Kolb, M. Kumari, R. Schreiber, S. Kolleritsch, P. Markolin, G. F. Grabner, C. Heier, K. A. Zierler, T. Rulicke, R. Zimmermann, A. Lass, R. Zechner, and G. Haemmerle. Cardiac-specific overexpression of perilipin 5 provokes severe cardiac steatosis via the formation of a lipolytic barrier. J. Lipid Res. 2013. 54: 1092-1102.

引用

页码：1092 / 1102

页数：11

共 43 条

[1] Distinct cellular pools of perilipin 5 point to roles in lipid trafficking [J].