LIPOPROTEIN COMPOSITION AND METABOLISM IN PIMA INDIANS

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Pima Indians have a high prevalence of obesity, diabetes mellitus and hyperinsulinemia, but they have low plasma cholesterol levels, reduced low density lipoprotein (LDL) and high density lipoprotein (HDL), and decreased incidence of cardiovascular disease (CVD). Lipoprotein composition and metabolism in Pima Indians are being investigated in order to further understand control of lipoprotein metabolism and how lipoproteins are related to obesity and CVD. The studies of lipoprotein composition indicate there may be racial differences in lipoprotein distributions which may be important in the prevalence of CVD. Simultaneous studies have been performed of very low density lipoprotein (VLDL) apoB and LDL apoB metabolism using a double isotope procedure. In addition, a multicompartmental model has been developed for the analysis of kinetic data for the simultaneous measure of VLDL, IDL and LDL apoB metabolism. Studies in a group of male Pimas indicated that obesity results in a greatly increased flux of VLDL apoB. LDL apoB levels were not elevated in the obese subjects, because of both increased metabolism of VLDL through the alternate pathway and increased catabolism of LDL. Comparison of apoB metabolism in Pimas and weight-matched Caucasians indicated that the low LDL in Pimas is related to both higher FCR for LDL and higher proportion of VLDL metabolized without conversion of LDL. Further, VLDL "shunt" and LDL FCR appeared to be correlated. The results of lipoprotein metabolic studies in Pimas to date suggest a large flux of substrates and regulators (i.g. insulin) which cause over production of lipoproteins, but that compensatory mechanisms are operative which result in maintenance of low plasma concentrations.