Regulatory Effects of HMG CoA Reductase Inhibitor and Fish Oils on Apolipoprotein B-100 Kinetics in Insulin-Resistant Obese Male Subjects With Dyslipidemia

  1. Dick C. Chan1,
  2. Gerald F. Watts1,
  3. P. Hugh R. Barrett1,
  4. Lawrence J. Beilin1,
  5. Trevor G. Redgrave2 and
  6. Trevor A. Mori1
  1. 1Department of Medicine, University of Western Australia and the Western Australian Institute for Medical Research, Crawley, Western Australia
  2. 2Department of Physiology, University of Western Australia, Crawley, Western Australia


    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.


    • Address correspondence and reprint requests to Prof. G.F. Watts, Department of Medicine, University of Western Australia, GPO Box X2213, Perth, Western Australia 6847. E-mail: gfwatts{at}

      Received for publication 18 March 2002 and accepted in revised form 3 May 2002.

      apo, apolipoprotein; apoB, apolipoprotein B-100; CVD, cardiovascular disease; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FCR, fractional catabolic rate; GLM, general linear model; HOMA, homeostasis model assessment; IDL, intermediate-density lipoprotein; NEFA, nonesterified fatty acid; PPAR, peroxisome proliferator-activated receptor; RLP, remnant-like particle; SREBP-1c, sterol regulatory element binding protein-1c.

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