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SHR Neuro Krebs Kardio Lipid

Kumari, M; Schoiswohl, G; Chitraju, C; Paar, M; Cornaciu, I; Rangrez, AY; Wongsiriroj, N; Nagy, HM; Ivanova, PT; Scott, SA; Knittelfelder, O; Rechberger, GN; Birner-Gruenberger, R; Eder, S; Brown, HA; Haemmerle, G; Oberer, M; Lass, A; Kershaw, EE; Zimmermann, R; Zechner, R.
Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase.
Cell Metab. 2012; 15(5):691-702 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Birner-Grünberger Ruth
Paar Margret

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Number of Figures: 7
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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.
Find related publications in this database (using NLM MeSH Indexing)
1-Acylglycerol-3-Phosphate O-Acyltransferase - genetics
Acyl Coenzyme A - genetics
Acyltransferases - genetics
Animals -
CHO Cells -
COS Cells -
Cercopithecus aethiops -
Cricetinae -
Cysteine Endopeptidases - genetics
Dietary Sucrose - metabolism
Fatty Liver - genetics
Hep G2 Cells -
Humans -
Lipid Metabolism - genetics
Lipids - biosynthesis
Liver - drug effects
Lysophospholipids - genetics
Male -
Membrane Proteins - genetics
Mice -
Mice, Knockout -
Models, Molecular -
Phosphatidic Acids - genetics
Phospholipids - genetics
Polymorphism, Genetic -
Triglycerides - genetics
Up-Regulation -

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