Adiponutrin Functions as a Nutritionally Regulated Lysophosphatidic Acid Acyltransferase

被引：260

作者：

Kumari, Manju ^{[1
]}

Schoiswohl, Gabriele ^{[1
,2
]}

Chitraju, Chandramohan ^{[1
]}

Paar, Margret ^{[1
]}

Cornaciu, Irina ^{[1
]}

Rangrez, Ashraf Y. ^{[3
]}

Wongsiriroj, Nuttaporn ^{[1
]}

Nagy, Harald M. ^{[1
]}

Ivanova, Pavlina T. ^{[4
]}

Scott, Sarah A. ^{[4
]}

Knittelfelder, Oskar ^{[1
]}

Rechberger, Gerald N. ^{[1
]}

Birner-Gruenberger, Ruth ^{[5
,6
]}

Eder, Sandra ^{[1
]}

Brown, H. Alex ^{[4
]}

Haemmerle, Guenter ^{[1
]}

Oberer, Monika ^{[1
]}

Lass, Achim ^{[1
]}

Kershaw, Erin E. ^{[2
]}

Zimmermann, Robert ^{[1
]}

Zechner, Rudolf ^{[1
]}

机构：

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

[2] Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA 15261 USA

[3] Univ Hosp Schleswig Holstein, Dept Internal Med Cardiol & Angiol 3, D-24105 Kiel, Germany

[4] Vanderbilt Univ, Sch Med, Dept Pharmacol & Chem, Nashville, TN 37232 USA

[5] Med Univ Graz, Med Res Ctr, A-8010 Graz, Austria

[6] Med Univ Graz, Inst Pathol, Prote Core Facil, A-8010 Graz, Austria

来源：

CELL METABOLISM | 2012年 / 15卷 / 05期

基金：

美国国家卫生研究院;

关键词：

FATTY LIVER-DISEASE; ADIPOSE TRIGLYCERIDE LIPASE; CONGENITAL GENERALIZED LIPODYSTROPHY; COMPARATIVE GENE IDENTIFICATION-58; CHANARIN-DORFMAN-SYNDROME; MESSENGER-RNA EXPRESSION; LIPID-METABOLISM; FAMILY-MEMBERS; PNPLA3; ENZYMES;

D O I：

10.1016/j.cmet.2012.04.008

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Numerous studies in humans link a nonsynonymous genetic polymorphism (I148M) in adiponutrin (ADPN) to various forms of fatty liver disease and liver cirrhosis. Despite its high clinical relevance, the molecular function of ADPN and the mechanism by which I148M variant affects hepatic metabolism are unclear. Here we show that ADPN promotes cellular lipid synthesis by converting lysophosphatidic acid (LPA) into phosphatidic acid. The ADPN-catalyzed LPA acyltransferase (LPAAT) reaction is specific for LPA and long-chain acyl-CoAs. Wild-type mice receiving a high-sucrose diet exhibit substantial upregulation of Adpn in the liver and a concomitant increase in LPAAT activity. In Adpn-deficient mice, this diet-induced increase in hepatic LPAAT activity is reduced. Notably, the I148M variant of human ADPN exhibits increased LPAAT activity leading to increased cellular lipid accumulation. This gain of function provides a plausible biochemical mechanism for the development of liver steatosis in subjects carrying the I148M variant.

引用

页码：691 / 702

页数：12

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