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

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 lipas e (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 HS L activity had any effect on lipid phenotype and if low HSL activity and FC HL were linked in Finnish FCHL families. A total of 48 family members from 13 well-characterized Finnish FCHL families and 12 unrelated spouses partic ipated in the study. FCHL patients with different lipid phenotypes (IIA, II B, IV) did not differ in adipose tissue HSL activity from each other or fro m the 12 normolipidemic spouses (P = 0.752). In parametric linkage analysis using an affecteds-only strategy the low adipose tissue HSL activity was n ot significantly linked with FCHL phenotype. However, we found a significan t sibling-sibling correlation for the HSL trait (0.51, P < 0.01). Thus, a m odifying or interacting role of HSL in the pathogenesis of FCHL could not b e excluded. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.