DGAT1 deficiency decreases PPAR expression and does not lead to lipotoxicity in cardiac and skeletal muscle

被引：68

作者：

Liu, Li ^{[1
]}

Yu, Shuiqing ^{[1
]}

Khan, Raffay S. ^{[1
]}

Ables, Gene P. ^{[1
]}

Bharadwaj, Kalyani G. ^{[1
]}

Hu, Yunying ^{[1
]}

Huggins, Lesley A. ^{[1
]}

Eriksson, Jan W. ^{[2
,3
]}

Buckett, Linda K. ^{[4
]}

Turnbull, Andrew V. ^{[4
]}

Ginsberg, Henry N. ^{[1
]}

Blaner, William S. ^{[1
]}

Huang, Li-Shin ^{[1
]}

Goldberg, Ira J. ^{[1
]}

机构：

[1] Columbia Univ, Div Prevent Med & Nutr, New York, NY 10027 USA

[2] Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden

[3] AstraZeneca R&D, Molndal, Sweden

[4] AstraZeneca R&D, Macclesfield, Cheshire, England

来源：

JOURNAL OF LIPID RESEARCH | 2011年 / 52卷 / 04期

基金：

美国国家卫生研究院;

关键词：

heart; triglyceride; diacylglycerol acyl transferase; ceramide; exercise; muscle hypertrophy; peroxisome proliferator-activated receptor; INDUCED INSULIN-RESISTANCE; COA-DIACYLGLYCEROL ACYLTRANSFERASE-1; WHITE ADIPOSE-TISSUE; PROTEIN-KINASE-C; FATTY-ACID OXIDATION; TRIGLYCERIDE SYNTHESIS; TRIACYLGLYCEROL SYNTHESIS; OBESITY RESISTANCE; GLUCOSE-METABOLISM; GLYCOGEN-SYNTHESIS;

D O I：

10.1194/jlr.M011395

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：

Diacylglycerol (DAG) acyl transferase 1 (Dgat1) knockout ((-/-)) mice are resistant to high-fat-induced obesity and insulin resistance, but the reasons are unclear. Dgat1(-/-) mice had reduced mRNA levels of all three Ppar genes and genes involved in fatty acid oxidation in the myocardium of Dgat1(-/-) mice. Although DGAT1 converts DAG to triglyceride (TG), tissue levels of DAG were not increased in Dgat1(-/-) mice. Hearts of chow-diet Dgat1(-/-) mice were larger than those of wild-type (WT) mice, but cardiac function was normal. Skeletal muscles from Dgat1(-/-) mice were also larger. Muscle hypertrophy factors phospho-AKT and phospho-mTOR were increased in Dgat1(-/-) cardiac and skeletal muscle. In contrast to muscle, liver from Dgat1(-/-) mice had no reduction in mRNA levels of genes mediating fatty acid oxidation. Glucose uptake was increased in cardiac and skeletal muscle in Dgat1(-/-) mice. Treatment with an inhibitor specific for DGAT1 led to similarly striking reductions in mRNA levels of genes mediating fatty acid oxidation in cardiac and skeletal muscle. These changes were reproduced in cultured myocytes with the DGAT1 inhibitor, which also blocked the increase in mRNA levels of Ppar genes and their targets induced by palmitic acid.jlr Thus, loss of DGAT1 activity in muscles decreases mRNA levels of genes involved in lipid uptake and oxidation.-Liu, L., S. Yu, R. S. Khan, G. P. Ables, K. G. Bharadwaj, Y. Hu, L. A. Huggins, J. W. Eriksson, L. K. Buckett, A. V. Turnbull, H. N. Ginsberg, W. S. Blaner, L-S. Huang, and I. J. Goldberg. DGAT1 deficiency decreases PPAR expression and does not lead to lipotoxicity in cardiac and skeletal muscle. J. Lipid Res. 2011. 52: 732-744.

引用

页码：732 / 744

页数：13

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