Adipose Triglyceride Lipase (ATGL) and Hormone-Sensitive Lipase (HSL) Deficiencies Affect Expression of Lipolytic Activities in Mouse Adipose Tissues

Maria Morak,Hannes Schmidinger,Gernot Riesenhuber,Gerald N Rechberger,Manfred Kollroser,Guenter Haemmerle,Rudolf Zechner,Florian Kronenberg,Albin Hermetter

doi:10.1074/mcp.m111.015743

Abstract

Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key enzymes involved in intracellular degradation of triacylglycerols. It was the aim of this study to elucidate how the deficiency in one of these proteins affects the residual lipolytic proteome in adipose tissue. For this purpose, we compared the lipase patterns of brown and white adipose tissue from ATGL (-/-) and HSL (-/-) mice using differential activity-based gel electrophoresis. This method is based on activity-recognition probes possessing the same substrate analogous structure but carrying different fluorophores for specific detection of the enzyme patterns of two different tissues in one electrophoresis gel. We found that ATGL-deficiency in brown adipose tissue had a profound effect on the expression levels of other lipolytic and esterolytic enzymes in this tissue, whereas HSL-deficiency hardly showed any effect in brown adipose tissue. Neither ATGL- nor HSL-deficiency greatly influenced the lipase patterns in white adipose tissue. Enzyme activities of mouse tissues on acylglycerol substrates were analyzed as well, showing that ATGL-and HSL-deficiencies can be compensated for at least in part by other enzymes. The proteins that responded to ATGL-deficiency in brown adipose tissue were overexpressed and their activities on acylglycerols were analyzed. Among these enzymes, Es1, Es10, and Es31-like represent lipase candidates as they catalyze the hydrolysis of long-chain acylglycerols.

Highlights

Excess lipids are stored as intracellular triacylglycerol and steryl ester deposits in animals, plant seeds, and fungi
That Adipose triglyceride lipase (ATGL)-deficiency in BAT had a profound effect on the expression levels of other lipolytic and esterolytic enzymes in this tissue, whereas hormone-sensitive lipase (HSL)-deficiency hardly showed any effect in BAT
The amounts of the fluorescent components were determined from their respective fluorescence intensities. It was the aim of this study to determine the effects of ATGL- and HSL-deficiency on the expression of other lipolytic activities in BAT and WAT

Summary

Introduction

Excess lipids are stored as intracellular triacylglycerol and steryl ester deposits in animals, plant seeds, and fungi. The different appearance of brown and white adipose tissue is caused by differences in lipid content and the abundance of mitochondria in the constituent adipocytes. The thermogenic activity of BAT is caused by the expression of one protein unique in brown adipocytes, the uncoupling protein 1 (UCP1). This polypeptide is a facultative proton transporter and localizes to the inner mitochondrial membrane. Impairment of lipolysis in adipocytes may be associated with clinical symptoms including obesity, insulin resistance, diabetes mellitus, and dyslipidaemia All these conditions seem to have a common substrate called lipotoxicity [7,8,9,10]. Recent functional proteomic screens in various mouse tissues led to the identification of enzyme candidates that are currently subject to functional characterization (unpublished data)

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