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Abstract: 136 NARINGENIN PREVENTS THE DYSLIPIDEMIA, APOB OVERPRODUCTION AND HYPERINSULINEMIA IN LDL-RECEPTOR NULL MICE WITH DIET-INDUCED INSULIN RESISTANCE
Workshop II-7 - Lipoprotein Metabolism: Integration of Lipoprotein Metabolism Abstract: 136 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
NARINGENIN PREVENTS THE DYSLIPIDEMIA, APOB OVERPRODUCTION AND HYPERINSULINEMIA IN LDL-RECEPTOR NULL MICE WITH DIET-INDUCED INSULIN RESISTANCE E Mulvihill, E Allister, B Sutherland, R Hegele, M Huff Robarts Research Institute, the University of Western Ontario, London, On The metabolic syndrome is an important predisposing factor for atherosclerosis and includes dyslipidemia characterized by hepatic overproduction of very low density lipoproteins (VLDL). Insulin resistance is central to the metabolic syndrome, however, few therapeutic strategies correct insulin resistance with normalization of dyslipidemia. Previously, we demonstrated that the citrus-derived flavonoid, naringenin inhibits VLDL apoB100 secretion from cultured hepatocytes in a manner resembling insulin. Naringenin, like insulin, reduces apoB secretion through intracellular degradation of apoB, mediated by PI3K and MAPKerk signaling. However, the effect of naringenin was independent of the insulin receptor. We report that combining naringenin with low insulin doses potentiated cell signaling, leading to greater reductions in apoB secretion, demonstrating that naringenin sensitizes cells to insulin. Naringenin treatment of Ldlr-/- mice fed a western diet, a model of the metabolic syndrome, corrected VLDL overproduction, ameliorated hepatic steatosis and attenuated dyslipidemia. Naringenin increased hepatic fatty acid oxidation through a Pgc1Į/PPARĮ-mediated transcription program. Naringenin prevented SREBP1c-induced lipogenesis in liver and muscle. By reducing both VLDL-derived and endogenous fatty acid synthesis, naringenin prevented muscle triglyceride accumulation and hyperinsulinemia, leading to improved insulin sensitivity and glucose tolerance. Thus, naringenin, through its insulin-like properties corrects many of the metabolic disturbances linked to insulin resistance. Funding: Heart and Stroke Foundation of Canada Canadian Institutes of Health Research
NARINGENIN PREVENTS THE DYSLIPIDEMIA, APOB OVERPRODUCTION AND HYPERINSULINEMIA IN LDL-RECEPTOR NULL MICE WITH DIET-INDUCED INSULIN RESISTANCE E Mulvihill, E Allister, B Sutherland, R Hegele, M Huff Robarts Research Institute, the University of Western Ontario, London, On The metabolic syndrome is an important predisposing factor for atherosclerosis and includes dyslipidemia characterized by hepatic overproduction of very low density lipoproteins (VLDL). Insulin resistance is central to the metabolic syndrome, however, few therapeutic strategies correct insulin resistance with normalization of dyslipidemia. Previously, we demonstrated that the citrus-derived flavonoid, naringenin inhibits VLDL apoB100 secretion from cultured hepatocytes in a manner resembling insulin. Naringenin, like insulin, reduces apoB secretion through intracellular degradation of apoB, mediated by PI3K and MAPKerk signaling. However, the effect of naringenin was independent of the insulin receptor. We report that combining naringenin with low insulin doses potentiated cell signaling, leading to greater reductions in apoB secretion, demonstrating that naringenin sensitizes cells to insulin. Naringenin treatment of Ldlr-/- mice fed a western diet, a model of the metabolic syndrome, corrected VLDL overproduction, ameliorated hepatic steatosis and attenuated dyslipidemia. Naringenin increased hepatic fatty acid oxidation through a Pgc1Į/PPARĮ-mediated transcription program. Naringenin prevented SREBP1c-induced lipogenesis in liver and muscle. By reducing both VLDL-derived and endogenous fatty acid synthesis, naringenin prevented muscle triglyceride accumulation and hyperinsulinemia, leading to improved insulin sensitivity and glucose tolerance. Thus, naringenin, through its insulin-like properties corrects many of the metabolic disturbances linked to insulin resistance. Funding: Heart and Stroke Foundation of Canada Canadian Institutes of Health Research