Fatty acid specificity of hormone-sensitive lipase: implication in the selective hydrolysis of triacylglycerols

Thierry Raclot,Cecilia Holm,Dominique Langin

doi:10.1016/s0022-2275(20)31534-0

Abstract

The selective mobilization of fatty acids from white fat cells depends on their molecular structure, in particular the degree of unsaturation. The present study was designed to examine if the release of fatty acids by hormone-sensitive lipase (HSL) in vitro i) is influenced by the amount of unsaturation, ii) depends on the temperature, and iii) could explain the selective pattern of fatty acid mobilization and notably the preferential mobilization of certain highly unsaturated fatty acids. Recombinant rat and human HSL were incubated with a lipid emulsion. The hydrolysis of 35 individual fatty acids, ranging in chain length from 12 to 24 carbon atoms and in unsaturation from 0 to 6 double bonds was measured. Fatty acid composition of in vitro released NEFA was compared with that of fat cell triacylglycerols (TAG), the ratio % NEFA/% TAG being defined as the relative hydrolysis. The relative hydrolysis of individual fatty acids differed widely, ranging from 0.44 (24:1n-9) to 1.49 (18:1n-7) with rat HSL, and from 0.38 (24:1n-9) to 1.67 (18:1n-7) with human HSL. No major difference was observed between rat and human HSL. The relative release was dependent on the number of double bonds according to chain length. The amount of fatty acid released by recombinant rat HSL was decreased but remained robust at 4 degrees C compared with 37 degrees C, and the relative hydrolysis of some individual fatty acids was affected. The relative hydrolysis of fatty acids moderately, weakly, and highly mobilized by adipose tissue in vivo was similar and close to unity in vitro. We conclude that i) the release of fatty acids by HSL is only slightly affected by their degree of unsaturation, ii) the ability of HSL to efficiently and selectively release fatty acids at low temperature could reflect a cold adaptability for poikilotherms or hibernators when endogenous lipids are needed, and iii) the selectivity of fatty acid hydrolysis by HSL does not fully account for the selective pattern of fatty acid mobilization, but could contribute to explain the preferential mobilization of some highly unsaturated fatty acids compared with others.

Highlights

The selective mobilization of fatty acids from white fat cells depends on their molecular structure, in particular the degree of unsaturation
Lipolysis is mainly achieved by hormone-sensitive lipase (HSL), which has a critical role in the control of energy homeostasis and catalyzes the rate-limiting step in the breakdown of adipocyte TAG [3]
This would be in line with a previous study in our laboratories showing that fatty acids are selectively hydrolyzed from TAG by HSL according to carbon atom chain length [6]

Summary

Introduction

The selective mobilization of fatty acids from white fat cells depends on their molecular structure, in particular the degree of unsaturation. The mobilization of fatty acids from white fat cells is selective and depends on the fatty acid chain length and unsaturation [4]. Among fatty acids usually found in adipose tissue TAG (12 to 24 carbon atoms and 0 to 6 double bonds), a fatty acid is more readily mobilized as its carbon chain is shorter and more unsaturated. From these results, fatty acids have been grouped into three categories by taking into account their relative mobilization rate, chain length, and unsaturation [5]. This would be in line with a previous study in our laboratories showing that fatty acids are selectively hydrolyzed from TAG by HSL according to carbon atom chain length [6]

Objectives

Methods

Results

Conclusion