Abstracts of the 5th International Conference of t

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Publish Date: 2008/03/27

Volume: 22, Issue: 2, Pages: 133-158

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Abstract

1 Cardiovascular Research Group and the 2 CIHR Group on the Molecular and Cell Biology of Lipids Depts of 1 Pediatrics and 2 Biochemistry Faculty fo Medicine and Dentistry University of Alberta Edmonton Alberta Canada 3 Department of Cell Biology Lerner Research Institute The Cleveland Clinic Foundation Cleveland Ohio USA 4 Baylor College of Medicine USDA/ARS Children’s Nutrition Research Center Houston Texas USA 5 Faculty of Pharmacy and Department of Pharmacology Faculty of Medicine Université de Montreal Montreal Quebec CanadaConsuming diets rich in fatty acids leading to excessive weight gain has been identified as a major contributor to the pathogenesis of Type 2 Diabetes T2D a known risk factor for cardiovascular disease Associated with dietinduced obesity DIO are elevated levels of plasma fatty acids FA and lipoprotein associated triglycerides TG Since the levels of plasma FA and lipoprotein associated TG are primarily controlled by the liver it is likely that aberrant hepatic FA uptake and handling contributes to the dyslipidemia that precedes development of T2D Indeed we have shown that mRNA and protein expression of the FA transport protein CD36 which is normally expressed at low levels in the mouse liver is significantly elevated during DIO and is correlated with increased hepatic TG storage and TG secretion as very lowdensity lipoproteins VLDL In vivo gene delivery of a recombinant adenovirus harboring CD36 cDNA AdCD36 into lean mice showed a significant increase in hepatic FA uptake in vivo and an accumulation in hepatic TG storage and VLDLTG secretion compared to AdNullinjected mice demonstrating that increased CD36 expression alone is sufficient to recapitulate the alterations in liver lipid storage and VLDLTG secretion observed in DIO Together these data show that increased hepatic CD36 expression may play a causative role in the dyslipidemia associated with DIO and further suggests that inhibition of hepatic CD36 may prove to be beneficial for the prevention of insulin resistance and the eventual development of T2DBackground Fish oil feeding increases incorporation of the omega3 polyunsaturated fatty acid n3 PUFA docosahexaenoic acid DHA 226n3 into both skeletal muscle and myocardial cell membranes and increases the efficiency of myocardial oxygen use 1

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