Adipose triglyceride lipase regulation of skeletal muscle lipid metabolism and insulin responsiveness.

Molecular Endocrinology
Matthew J WattBruce E Kemp

Abstract

Adipose triglyceride lipase (ATGL) is important for triglyceride (TG) metabolism in adipose tissue, and ATGL-null mice show increased adiposity. Given the apparent importance of ATGL in TG metabolism and the association of lipid deposition with insulin resistance, we examined the role of ATGL in regulating skeletal muscle lipid metabolism and insulin-stimulated glucose disposal. ATGL expression in myotubes was reduced by small interfering RNA and increased with a retrovirus encoding GFP-HA-ATGL. ATGL was also overexpressed in rats by in vivo electrotransfer. ATGL was down-regulated in skeletal muscle of obese, insulin-resistant mice and negatively correlated with intramyocellular TG levels. ATGL small interfering RNA in myotubes reduced TG hydrolase activity and increased TG content, whereas ATGL overexpression induced the reciprocal response, indicating that ATGL is an essential TG lipase in skeletal muscle. ATGL overexpression in myotubes increased the oxidation of fatty acid liberated from TG and diglyceride and ceramide contents. These responses in cells were largely recapitulated in rats overexpressing ATGL. When ATGL protein expression and TG hydrolase activity in obese, insulin-resistant rats were restored to levels obse...Continue Reading

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Citations

Apr 25, 2009·The Journal of Biological Chemistry·Marie-Line PeyotMarc Prentki
Nov 7, 2008·Clinical and Experimental Pharmacology & Physiology·Matthew J Watt
May 19, 2009·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Matthew J Watt
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