Studies on Metabolic Syndrome and Diabetes-Accelerated Atherosclerosis: a Metabolomic Approach

The multiple risk factors that describe metabolic syndrome also predict a higher incidence of type 2 diabetes mellitus and atherosclerotic cardiovascular disease (CVD). The underlying mechanisms that trigger metabolic syndrome include insulin resistance, dyslipidemia, obesity, and inflammation. Specific animal models and human subjects, when subjected to a high-fructose high-calorie diet may induce hypertriglyceridemia, insulin resistance, obesity, and hypertension, namely metabolic syndrome. However, the underlying interactions among multiple risk factors and mechanisms leading to the disturbances in metabolite profiling such as in gluconeogenesis, lipid metabolism (especially hepatic and plasma TG, higher plasma FFAs, and lower HDL-C) and feasibility of metabolite profiles as biomarkers of metabolic syndrome and diabetes-accelerated atherosclerosis remain to be elucidated. As an emerging filed in the post-genomic era, metabolomics is defined as the study of low-molecular-weight metabolite profiling, an approach particularly attractive as an alternative and complementary tool in the studies of degenerative diseases. Lipidomics is a branch of metabolomics. It is a systems-based study of all lipid metabolites, the molecules with which the lipids interact, and their functions in physiological states and dysfunction in pathophysiological states. The aim of this three-year project is to dissect the interaction and contribution of the multiple risk factors in disease progression, starting from metabolic syndrome, diabetes, and diabetes-accelerated atherosclerosis in animal models. Metabolomic tools will be incorporated as a major approach. The animal studies are based on an early, initiation stage (metabolic syndrome) and an advanced, disease-promoting stage (diabetes-accelerated atherosclerosis). High-fructose, high-calorie diet-fed male SD rats and STZ-treated apolipoprotein E-deficient mice will be used as the pathophysiological animal models, respectively. It is anticipated that a portfolio of biomarkers, correlating with a global metabolite profiling, that better describe the progression and severity of diseases will be obtained, if the proposal is supported and goal is achieved.

Project ID:PC10001-0094
External Project ID:NSC98-2314-B182-009-MY3