Down-regulation of hepatic lipase expression in experimental nephrotic syndrome

Abstract

Hepatic lipase (HL) plays an important role in catabolism of chylomicron remnants, conversion of intermediate density lipoprotein (IDL) to low-density lipoprotein (LDL) and reverse transport of cholesterol to the liver. Several features of the nephrotic dyslipidemia point to the possible presence of HL deficiency. In an attempt to address this possibility, gene expression of HL was studied in rats with puromycin-induced nephrotic syndrome (NS). The results were compared with those obtained in a group of placebo-treated control animals. The NS group showed marked proteinuria, hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia, normal creatinine clearance and normal hepatic tissue cholesterol concentration. HL activity of the liver tissue was reduced by approximately 60% in the NS group as compared to that found in the normal control group. The reduction of HL activity in the NS group was accompanied by a reduction of HL mRNA of virtually similar magnitude. HL activity of the liver tissue was inversely related to urinary protein excretion, serum cholesterol and serum triglyceride concentrations. In contrast, HL activity was directly related to serum albumin concentration and HL mRNA. No significant difference was observed in HL activity between the control group and the pre-nephrotic animals studied at days 1 and 5 following puromycin administration. This observation excludes an acute effect of puromycin as a possible cause of HL deficiency in the NS animals. Thus, NS in this model results in a marked down-regulation of HL expression which may, in part, contribute to the nephrotic dyslipidemia.