Donna F Vine, Ye Wang, Danni Shi and Spencer D Proctor
The metabolic syndrome is highly associated with the incidence of Polycystic Ovary Syndrome (PCOS). The metabolic aberrations of insulin resistance and hyperandrogenemia have been proposed to contribute to the development of dyslipidemia and increased Cardiovascular Disease (CVD) risk in PCOS. The contribution of nonfasting intestinal lipemia to CVD risk is well established, however little is known regarding the role of androgens in regulating these pathways in conditions of the metabolic syndrome and PCOS. The aim of this study was to determine the contribution of the intestine to lipemia, and the relationship with serum testosterone and insulin in the JCR: LA-cp rodent model of the metabolic syndrome and PCOS. Fasting and non-fasting plasma lipid and intestinal apolipoprotein (apo) B- metabolism were measured in the fasting state, and non-fasting state in response to a highfat meal. In addition, intestinal mesenteric lymph cannulation was used to determine the intestinal secretion of apoBlipoproteins and associated lipids. The PCOS-like genotype was observed to have elevated fasting and non-fasting plasma triglyceride, cholesterol and apo-B48 (a marker of intestinal-derived apoB-lipoproteins) compared to control animals. Intestinal lymphatic secretion of apoB48-lipoproteins, triglyceride and cholesterol were elevated in the fasted and non-fasted state. Serum total testosterone and insulin were shown to be positively correlated with fasting and non-fasting plasma triglyceride and apoB48 concentrations. In conclusion, the intestinal oversecretion of apo- B48 lipoproteins and lipids contributes to dyslipidemia in the JCR: LA-cp rodent model of the metabolic syndrome and PCOS. This model may be used to further our understanding of the pathophysiology of dyslipidemia and CVD risk in conditions of hyperandrogenemia and insulin resistance in PCOS.
