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.