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

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Chan DC, Watts GF, Barrett PH, Beilin LJ, Redgrave TG, Mori TA

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

Diabetes. 2002 Aug;51(8):2377-86.

PubMed ID

12145148 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Pharmaco-metabolomics

Drug	Drug Groups	Metabolite	Change	Description
Atorvastatin	Approved	Non-HDL cholesterol	decreased	Atorvastatin decreases the level of Non-HDL cholesterol in the blood
Omega-3-acid ethyl esters	Approved Investigational	Triglycerides	decreased	Omega-3-acid ethyl esters decreases the level of Triglycerides in the blood
Atorvastatin	Approved	Lathosterol	decreased	Atorvastatin decreases the level of Lathosterol in the blood
Omega-3-acid ethyl esters	Approved Investigational	HDL cholesterol	increased	Omega-3-acid ethyl esters increases the level of HDL cholesterol in the blood
Atorvastatin	Approved	Remnant-like particle cholesterol	decreased	Atorvastatin decreases the level of Remnant-like particle cholesterol in the blood
Atorvastatin	Approved	Total cholesterol	decreased	Atorvastatin decreases the level of Total cholesterol in the blood
Atorvastatin	Approved	Triglycerides	decreased	Atorvastatin decreases the level of Triglycerides in the blood
Atorvastatin	Approved	LDL cholesterol	decreased	Atorvastatin decreases the level of LDL cholesterol in the blood