Regulatory effects of HMG CoA reductase inhibitor and fish oils on apolipoprotein B-100 kinetics in insulin-resistant obese male subjects with dyslipidemia

Hepatic accumulation of lipid substrates perturbs apolipoproteinB-100 (apoB) metabolism in insulin-resistant, obese subjects and may account for increased risk of cardiovascular disease. In a placebo-controlled trial, we examined the independent and combined effects of decreasing cholesterol synthesis with atorvastatin (40 mg/day) and triglyceride synthesis with fish oils (4 g/day) on apoB kinetics. The subjects were 48 viscerally obese, insulin-resistant men with dyslipidemia who were studied in a fasted state. We found that atorvastatin significantly. decreased plasma apoB-containing lipoproteins (P < 0.001, main effect) through increases in the fractional catabolic rate (FCR) of VLDL-, IDL-, and LDL-apoB (P < 0.01). Fish oils significantly decreased plasma levels of triglycerides and VLDL-apoB (P < 0.001), decreased the VLDL-apoB secretion rate (P < 0.01), but increased the conversion of VLDL to LDL (P < 0.001). Compared with placebo, combined treatment with atorvastatin and fish oils decreased VLDL-apoB secretion (P < 0.03) and increased the FCR of apoB in each lipoprotein fraction (P < 0.03) and the percent conversion of VLDL to LDL (P < 0.05). None of the treatments altered insulin resistance. In conclusion, in visceral obesity, atorvastatin increased hepatic clearance of all apoB-containing lipoproteins, whereas fish oils decreased hepatic secretion of VLDL-apoB. The differential effects of atorvastatin and fish oils on apoB kinetics support their combined use in correcting defective apoB metabolism in obese, insulin-resistant subjects.