Mitochondrial function and insulin resistance: role of fatty acids and physical activity

Abstract

Insulin resistance is observed in several conditions, such as obesity and diabetes mellitus type 2. Increased free fatty acid (FFA) concentration in the plasma is also present in these conditions. It has been postulated the involvement of these metabolites in the establishment of the insulin resistance. However, the involved mechanisms are not completely known. Recent studies suggest that FFA can impair mitochondrial function in skeletal muscle cells. Thus, this study will evaluate if the FFA-induced insulin resistance is associated to mitochondrial dysfunction. Moreover, it will be investigated if interventions such as regular physical activity and treatment with omega-3 polyunsaturated FFA prevent and/or revert the insulin resistance induced by saturated FFA. For that, culture of rat skeletal muscle cells will be submitted to the treatment with 50-200 microM of different FFA (caprylic, palmitic, stearic, oleic, linoleic, eicosapentaenoic and docosahexanoic) or to the electrical stimulation (1 h per day, during three consecutive days). After this period, insulin response (glucose metabolism and insulin signaling) and mitochondrial function (electrical polarity of the internal mitochondrial membrane and generation and content of ATP) will be evaluated. Glucose metabolism will be evaluated using [U-14C]D-glucose and 2-deoxy-[2,6-3H]D-glucose. Electrical polarity of the internal mitochondrial membrane will be investigated using rhodamine 123. Cytoplasmic ATP generation will be determined by luminescence through the assay of luciferase transfection. Prevention and/or reversion of saturated FFA-induced insulin resistance by regular electrical stimulation and omega-3 polyunsaturated FFA will be also evaluated. Thus, this study will determine not only the involvement of mitochondrial dysfunction in the physiopatology of saturated FFA-induced insulin resistance, but also possible preventive and/or therapeutically interventions such as regular physical activity and diet with FFA polyunsaturated omega-3. (AU)