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Letting lipids go: hormone-sensitive lipase

Haemmerle, Guenter; Zimmermann, Robert; Zechner, Rudolf

Current Opinion in Lipidology: June 2003 - Volume 14 - Issue 3 - p 289-297
Lipid metabolism

Purpose of review Despite their pathophysiological importance, the molecular mechanisms and enzymatic components of lipid mobilization from intracellular storage compartments are insufficiently understood. The aim of this review is to evaluate the role of hormone-sensitive lipase in this process.

Recent findings Hormone-sensitive lipase exhibits a broad specificity for lipid substrates such as triglycerides, diglycerides, cholesteryl esters, and retinyl esters and the enzyme is in a wide variety of tissues. The high enzyme activity in adipose tissue was considered rate-limiting in the degradation of stored triglycerides. This view of a single enzyme controlling the catabolism of stored fat was challenged by recent findings that in hormone-sensitive lipase deficient mice adipose tissue triglycerides were still hydrolyzed and that these animals were leaner than normal mice. These results indicated that in adipose tissue hormone-sensitive lipase cooperates with other yet unidentified lipases to control the mobilization of fatty acids from cellular depots and that this process is coordinately regulated with lipid synthesis. Induced mutant mouse lines that overexpress or lack hormone-sensitive lipase also provided evidence that hormone-sensitive lipase-mediated cholesteryl ester hydrolysis is involved in steroid-hormone production in adrenals and affects testis function. Finally, hormone-sensitive lipase deficiency in mice results in a lipoprotein profile characterized by low triglyceride and VLDL levels and increased HDL cholesterol concentrations.

Summary The ‘anti-atherosclerotic’ plasma lipoprotein profile and the fact that hormone-sensitive lipase deficient animals become lean identifies the inhibition of hormone-sensitive lipase as a potential target for the treatment of lipid disorders and obesity.

Institute of Molecular Biology, Biochemistry and Microbiology, Karl-Franzens University, Graz, Austria

Correspondence to Rudolf Zechner PhD, Institute of Molecular Biology, Biochemistry and Microbiology, Karl-Franzens University, Graz, Heinrichstrasse 31, A-8010 Graz, Austria Tel: +43 316 380 1909; Fax: +43 316 380 9016; e-mail: rudolf.zechner@uni-graz.at

© 2003 Lippincott Williams & Wilkins, Inc.