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Abstract: 67 CHARACTERISTICS OF CIRCULATING VLDL RESULTING FROM INSULIN RESISTANCE AND FATTY LIVER
Workshop I-7 - Lipoprotein Metabolism: Joint IAS-EAS Workshop "Hepatic Apolipoprotein B Metabolism" Abstract: 67 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
CHARACTERISTICS OF CIRCULATING VLDL RESULTING FROM INSULIN RESISTANCE AND FATTY LIVER L Schreier Lab. Of Lipids and Lipoproteins, Faculty of Pharmacy and Biochemistry,University of Buenos Aires, Buenos Aires The close association between non alcoholic fatty liver and insulin resistance (IR) is widely recognized. While the former is characterized by excessive intrahepatic TG accumulation, the latter induces an overproduction of VLDL particles. It has not been well elucidated whether these opposite mechanisms impact on VLDL characteristics or not. VLDL fraction isolated from IR patients presenting severe steatosis showed higher proportion of apoB: 4.9±2.8 mg/dl vs 1.8±0.5 p=0.01, being evident an increase in particle number which in turn correlated with free fatty acid (FFA) level, r=0.50 p=0.016. A decrease in adiponectin was associated to increased FFA r=-0.39 p=0.03 and apoB-VLDL, r=-0.44 p=0.03. Although fat accumulates in the liver of IR patients, an increased number of VLDL particles are being secreted promoted by high FFA flux. Increased TNFĮ and decreased adiponectin are signs of a proinflammatory state more pronounced in IR coexisting with fatty liver and linked to VLDL overproduction/secretion. In addition, rats fed by sucrose rich diet (SRD) as an IR model, allow evaluating VLDL produced in a fatty liver. VLDL secretion rate assay showed an increase in SRD p<0.02, confirming an overproduction despite the liver fat accumulation. VLDL chemical composition showed higher TG % p<0.02. Both, FFA levels and liver fat content correlated with VLDL-TG, r=0.49 and 0.55 respectively, p<0.030. Rats are naturally deficient in CETP, so circulating VLDL composition would represent the native VLDL synthesized and secreted. Hepatic lipid content would constitute an important determinant of secretion of TG enriched and probably large VLDL; both features would increase its atherogenic potential. Funding: Grants from UBA and ANPCyT.
CHARACTERISTICS OF CIRCULATING VLDL RESULTING FROM INSULIN RESISTANCE AND FATTY LIVER L Schreier Lab. Of Lipids and Lipoproteins, Faculty of Pharmacy and Biochemistry,University of Buenos Aires, Buenos Aires The close association between non alcoholic fatty liver and insulin resistance (IR) is widely recognized. While the former is characterized by excessive intrahepatic TG accumulation, the latter induces an overproduction of VLDL particles. It has not been well elucidated whether these opposite mechanisms impact on VLDL characteristics or not. VLDL fraction isolated from IR patients presenting severe steatosis showed higher proportion of apoB: 4.9±2.8 mg/dl vs 1.8±0.5 p=0.01, being evident an increase in particle number which in turn correlated with free fatty acid (FFA) level, r=0.50 p=0.016. A decrease in adiponectin was associated to increased FFA r=-0.39 p=0.03 and apoB-VLDL, r=-0.44 p=0.03. Although fat accumulates in the liver of IR patients, an increased number of VLDL particles are being secreted promoted by high FFA flux. Increased TNFĮ and decreased adiponectin are signs of a proinflammatory state more pronounced in IR coexisting with fatty liver and linked to VLDL overproduction/secretion. In addition, rats fed by sucrose rich diet (SRD) as an IR model, allow evaluating VLDL produced in a fatty liver. VLDL secretion rate assay showed an increase in SRD p<0.02, confirming an overproduction despite the liver fat accumulation. VLDL chemical composition showed higher TG % p<0.02. Both, FFA levels and liver fat content correlated with VLDL-TG, r=0.49 and 0.55 respectively, p<0.030. Rats are naturally deficient in CETP, so circulating VLDL composition would represent the native VLDL synthesized and secreted. Hepatic lipid content would constitute an important determinant of secretion of TG enriched and probably large VLDL; both features would increase its atherogenic potential. Funding: Grants from UBA and ANPCyT.