Soy intake has been documented to decrease blood lipid levels, improve overall arterial status, and improve insulin resistance. The physiological mechanisms by which soy improves blood lipid and glucose profiles is not known. Soy contains several different components including protein, soy lipids, fiber, and other phytochemicals including isoflavones. It is unclear if one or more of these fractions contribute to the beneficial properties of soy. Our research focused on the effect of soy isoflavones and the risk of developing atherosclerosis and other symptoms of metabolic syndrome.
Metabolic Syndrome is a pre-diabetic state characterized by dyslipidemia, insulin resistance, obesity, and hypertension. Some of the complications resulting from metabolic syndrome include cardiovascular disease and diabetes. Macrophages and the liver are an integral factor in the development of cardiovascular disease and diabetes. Macrophages exposed to high blood lipids become foam cells and contribute to heart disease by imbedding into vessel walls leading to fatty streaks, plaque formation, and atherosclerosis. The liver is the main site of glucose and lipid metabolism and has a major impact on the overall metabolic homeostasis of the body.
My project is focused on the hypothesis that soy isoflavones are activating PPARs (peroxisome-proliferator activated receptors). PPARs are nuclear receptors that activate genes involved in cellular lipid and glucose homeostasis. We have found that soy isoflavones up-regulate PPAR-regulated activity explaining, at least in part, the effect of soy intake on lipid and glucose metabolism. Furthermore, my research also shows that the soy isoflavones genistein and daidzein potentiate the effect of the hypolipidemic medication clofibrate (a PPARá ligand) and the insulin-sensitizing medication pioglitazone (a PPARã ligand) potentially increasing the efficacy of these medications. In vivo, soy isoflavones also ameliorate some of the symptoms associated with atherosclerosis in both PPARá wild-type mice and PPARá KO mice. Therefore, soy isoflavones may be affecting other PPARá-independent pathways such as PPARã. Taken together, the isoflavones are able to activate the PPARá and PPARã pathway although the overall physiological significance of these activations is complex and has yet to be fully characterized.
