Effect of nicotinic acid on plasma lipid and hepatic gene expression in obese insulin resistant dogs.

Abstract

Nicotinic acid (NA) is well known for improving plasma lipids in man (decrease in triglycerides (TG), total (TC) and LDL‐cholesterol (LDL‐C) and increase in HDL‐cholesterol (HDL‐C) levels). The aim of this study was to assess the effects of NA in obese insulin resistant dogs.Eight beagle dogs were alloted to 2 groups : treated (n=5) and control (n=3). Treated dogs were given 375mg/d of NA for one week and then 500mg/d for 3 weeks. Insulin sensitivity, plasma TG, TC, free fatty acids and insulinemia were assessed at the end of the experimental period. Plasma lipoproteins were separated, and LDL‐C or HDL‐C were measured. Hepatic expression of ABCA1 and SR‐BI was quantified using real‐time RT‐PCR.NA treatment did not induce any change in either insulin sensitivity or glycemia, insulinemia and free fatty acid concentrations. In the treated group, TG were reduced by 30% (p < 0.05), and TC by 25% (p < 0.001). Analysis of lipoprotein cholesterol showed a reduction in LDL‐C (p < 0.05) whereas HDL‐C was unchanged. All these parameters were unchanged in the control group. No change in the ABCA1 and SR‐BI expression was observed in liver.Our results confirm the effects of NA that have been described in humans, except that concerning the increase in HDL‐C. According to observations recently done in mice, as dogs are devoid of CETP activity, we can hypothesize that CETP might be the link between plasma TG decrease and change in HDL‐C.