Reduced hormone-sensitive lipase activity is not a major metabolic defect in Finnish FCHL families

Abstract The pathogenetic mechanisms behind familial combined hyperlipidemia (FCHL) are unknown. However, exaggerated postprandial lipemia and excessive serum free fatty acid (FFA) concentrations have drawn attention to altered lipid storage and lipolysis in peripheral adipose tissue. Hormone-sensitive lipase (HSL) is the enzyme responsible for intracellular lipolysis in adipocytes and a decrease of adipocyte HSL activity has been demonstrated in Swedish FCHL subjects. The aim of the study was to investigate if adipose tissue HSL activity had any effect on lipid phenotype and if low HSL activity and FCHL were linked in Finnish FCHL families. A total of 48 family members from 13 well-characterized Finnish FCHL families and 12 unrelated spouses participated in the study. FCHL patients with different lipid phenotypes (IIA, IIB, IV) did not differ in adipose tissue HSL activity from each other or from the 12 normolipidemic spouses ( P =0.752). In parametric linkage analysis using an affecteds-only strategy the low adipose tissue HSL activity was not significantly linked with FCHL phenotype. However, we found a significant sibling–sibling correlation for the HSL trait (0.51, P 0.01 ). Thus, a modifying or interacting role of HSL in the pathogenesis of FCHL could not be excluded.