Overexpression of hormone-sensitive lipase prevents triglyceride accumulation in adipocytes.

Abstract

IntroductionHormone-sensitive lipase (HSL) is a cytosolic neutral lipase that hydrolyzes intracellular stores of triglycerides within adipocytes and is thought to be the rate limiting enzyme in lipolysis; however, direct evidence to prove this concept has been lacking. The present study was designed to establish the function of HSL in adipocytes. A 2360-bp fragment containing the entire HSL coding region was cloned into the vector pCEP4 and was used to transfect the 3T3-F442A adipogenic cell line. Free fatty acids are a major energy source for most tissues. Circulating FFA in plasma are derived from the breakdown of stored triacylglycerols in adipose tissue (1, 2). It has been suggested that an increased metabolic activity (i.e., a greater release of FFA) of internal fat depots is responsible for the observations linking central obesity with an increased prevalence of hyperlipidemia, atherosclerosis, diabetes mellitus, insulin resistance, and hypertension (3, 4, 5). The major enzyme responsible for the mobilization of FFA from adipose tissue is thought to be hormone-sensitive lipase (HSL),' whose name was coined to reflect the ability of hormones such as catecholamines, ACTH, and glucagon to stimulate the activity of this intracellular neutral lipase (6). HSL catalyzes the first, rate-limiting step in lipolysis by cleaving the first ester-bond of triacylglycerols (7,8). In adipose tissue, HSL also catalyzes the second step of the lipolytic reaction by hydrolyzing diacylglycerol to monoacylglycerol (7,8). Although HSL is capable of hydrolyzing monoacylglycerols to FFA, the final step of the lipolytic process is carried out by another enzyme, monoacylglycerol lipase (9, 10). This is due to the specificity of HSL for 1,(3)-monoacylglycerols, while the main product of the hydrolysis of triacylglycerols is 2-monoacylglycerol (11). Indeed, the findings that monoacylglycerol accumulates in vitro in the presence of HSL when monoacylglycerol lipase is absent- (10)

Developmental patterns of FASN and LIPE mRNA expression in adipose tissue of growing Jinhua and Landrace gilts

“…LIPE is an adipocyte enzyme that cleaves fatty acids from intracellular triacylglycerol (Mersmann, 1998), and an increase in LIPE could depress the accumulation of triglycerol in adipose cells (Thompson et al, 1993;Sztalryd et al, 1995). In the present study, there was no obvious relationship between LIPE expression and carcass fat content in the two breeds, but there was a significant positive relationship between carcass fat content and the ratio of FASN to LIPE mRNA.…”

Lipolysis in the Absence of Hormone-Sensitive Lipase

“…It is also possible that it takes a longer time to develop adipocyte hypertrophy in mice than in in vitro cell culture experiments. In this context, it is noteworthy that 3T3-F442A cells, which overexpressed HSL, are depleted of fats and are defective in differentiation as indicated by reduced expression of the late markers of adipocyte differentiation, aP2, and glycerol-3-phosphate dehydrogenase (27).…”

The HIV protease inhibitor saquinavir impairs lipid metabolism and glucose transport in cultured adipocytes

“…The increased release of non-esterified fatty acids plays a central role in insulin resistance (Kelley & Simoneau 1994, Unger 1995. In addition, an elevated expression of HSL in adipocytes led to reduced adipose lipid accumulation, along with the delayed expression of late markers of adipocyte differentiation (Sztalryd et al 1995). Thus, the control of adipose tissue lipid accumulation may result in alterations in expression of other adipose tissue genes.…”