Growth Retardation, Impaired Triacylglycerol Catabolism, Hepatic Steatosis, and Lethal Skin Barrier Defect in Mice Lacking Comparative Gene Identification-58 (CGI-58)

被引：157

作者：

Radner, Franz P. W. ^{[1
]}

Streith, Ingo E. ^{[1
]}

Schoiswohl, Gabriele ^{[1
]}

Schweiger, Martina ^{[1
]}

Kumari, Manju ^{[1
]}

Eichmann, Thomas O. ^{[1
]}

Rechberger, Gerald ^{[1
]}

Koefeler, Harald C. ^{[2
]}

Eder, Sandra ^{[1
]}

Schauer, Silvia ^{[3
]}

Theussl, H. Christian ^{[4
]}

Preiss-Landl, Karina ^{[1
]}

Lass, Achim ^{[1
]}

Zimmermann, Robert ^{[1
]}

Hoefler, Gerald ^{[3
]}

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-8010 Graz, Austria

[3] Med Univ Graz, Inst Pathol, A-8010 Graz, Austria

[4] Inst Mol Pathol, A-1030 Vienna, Austria

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2010年 / 285卷 / 10期

基金：

奥地利科学基金会;

关键词：

HORMONE-SENSITIVE LIPASE; LIPID STORAGE DISEASE; ADIPOSE TRIGLYCERIDE LIPASE; CHANARIN-DORFMAN-SYNDROME; INSULIN-RESISTANCE; PROTEIN; OBESITY; MOBILIZATION; EXPRESSION; LIPOLYSIS;

D O I：

10.1074/jbc.M109.081877

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：

Comparative gene identification-58 (CGI-58), also designated as alpha/beta-hydrolase domain containing-5 (ABHD-5), is a lipid droplet-associated protein that activates adipose triglyceride lipase (ATGL) and acylates lysophosphatidic acid. Activation of ATGL initiates the hydrolytic catabolism of cellular triacylglycerol (TG) stores to glycerol and nonesterified fatty acids. Mutations in both ATGL and CGI-58 cause "neutral lipid storage disease" characterized by massive accumulation of TG in various tissues. The analysis of CGI-58-deficient (Cgi-58(-/-)) mice, presented in this study, reveals a dual function of CGI-58 in lipid metabolism. First, systemic TG accumulation and severe hepatic steatosis in newborn Cgi-58(-/-) mice establish a limiting role for CGI-58 in ATGL-mediated TG hydrolysis and supply of nonesterified fatty acids as energy substrate. Second, a severe skin permeability barrier defect uncovers an essential ATGL-independent role of CGI-58 in skin lipid metabolism. The neonatal lethal skin barrier defect is linked to an impaired hydrolysis of epidermal TG. As a consequence, sequestration of fatty acids in TG prevents the synthesis of acylceramides, which are essential lipid precursors for the formation of a functional skin permeability barrier. This mechanism may also underlie the pathogenesis of ichthyosis in neutral lipid storage disease patients lacking functional CGI-58.

引用

页码：7300 / 7311

页数：12

共 47 条

[1] AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34 [J].