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.
Chan
Dick C
DC
Department of Medicine, University of Western Australia and the Western Australian Institute for Medical Research, Crawley, Western Australia.
Watts
Gerald F
GF
Barrett
P Hugh R
PH
Beilin
Lawrence J
LJ
Redgrave
Trevor G
TG
Mori
Trevor A
TA
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000097:blood*; D000069059:Atorvastatin; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D001835:Body Weight; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005395:Fish Oils / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D010919:Placebos; D011758:Pyrroles / Q000627:therapeutic use*
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005395:Fish Oils; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D010919:Placebos; D011758:Pyrroles; D000069059:Atorvastatin