Hormone-sensitive lipase expression and activity in relation to lipolysis in human fat cells

Valérie Large,Peter Arner,Signy Reynisdottir,Jacques Grober,Vanessa Van Harmelen,Cecilia Holm,Dominique Langin

doi:10.1016/s0022-2275(20)32199-4

Abstract

Hormone-sensitive lipase (HSL) catalyzes the rate-limiting step in adipocyte lipolysis. The activity of HSL is thought to be primarily regulated by reversible phosphorylation. However, the regulation of HSL activity by pretranslational mechanisms has been poorly studied. The present studies were undertaken to explore the relationship between the levels of HSL protein and mRNA expressions and the lipolytic capacity. The study was performed in human abdominal subcutaneous adipocytes with identical sizes but having either a high (HL) or low (LL) lipolytic capacity (n = 16). Basal and maximal lipolysis induced by catecholamines, an adenylyl cyclase activator forskolin, and a cyclic AMP analogue dibutyryl cAMP were 50% lower in LL- in comparison with HL-fat cells (P < 0.05 or better). No differences in drug sensitivity were found. HSL activity and quantity were about 50% lower in LL- compared with HL-fat cells (P < 0.05). Moreover, the mRNA ratio between HSL and γ-actin was 35% lower in LL-compared with HL-fat cells (P < 0.05). There was a strong linear correlation between the protein and enzymatic HSL measurements (r2 = 0.91). In addition, the maximum lipolytic capacity was significantly correlated with HSL activity (r2 = 0.75) and HSL protein amount (r2 = 0.64).▪ It is concluded that hormone-sensitive lipase (HSL) expression, measured either as total HSL protein by Western blot analysis or as total amount of activatable HSL enzyme, is a major determinant of the maximum lipolytic capacity of human fat cells. In addition, HSL protein expression is at least, in part, determined by HSL mRNA expression.—Large, V., P. Arner, S. Reynisdottir, J. Grober, V. Van Harmelen, C. Holm, and D. Langin. Hormone-sensitive lipase expression and activity in relation to lipolysis in human fat cells.

Highlights

Hormone-sensitive lipase (HSL) catalyzes the rate-limiting step in adipocyte lipolysis
We have investigated the relationship between HSL activity, protein and mRNA levels, function, and lipolysis in human abdominal subcutaneous adipocytes from two groups of subjects with either a high or low maximum lipolytic capacity per cell
We demonstrated that HSL activity is not significantly different in the same subject when measured on tissue that had been frozen at Ϫ70ЊC compared to when measured on fresh tissue

Summary

Introduction

Hormone-sensitive lipase (HSL) catalyzes the rate-limiting step in adipocyte lipolysis. It is concluded that hormone-sensitive lipase (HSL) expression, measured either as total HSL protein by Western blot analysis or as total amount of activatable HSL enzyme, is a major determinant of the maximum lipolytic capacity of human fat cells. Hormone-sensitive lipase expression and activity in relation to lipolysis in human fat cells. A decrease in maximally stimulated lipolysis was shown in fat cells of patients with familial combined hyperlipidemia [6] and in subjects with heredity for obesity [7] These lipolytic defects were associated with a decrease in HSL enzyme activity. As there is no satisfactory method to directly probe the proportion of Hormone-sensitive lipase (HSL) is the enzyme responsible for the hydrolysis of triacylglycerol from the lipid droplet of adipocytes into glycerol and non-esterified fatty acids [1].

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Conclusion