Abstract
Introduction: Obesity leads to insulin resistance and type 2 diabetes. Taking advantage of the existence of different subgroups of insulin sensitivity levels in obese population, we compared metabolic and inflammation parameters both at systemic and skeletal muscle (SM) levels in normal weight insulin –sensitive (CT), obese insulin-sensitive (OIS) and obese insulin-resistant (OIR) post-menopausal women. We observed an over-activation of Akt in OIR SM. The Akt signaling system is a central pathway that controls SM mass, protein synthesis and proteolysis. So, we have been interested in evaluating the impact of the over-activation of Akt on the regulation of muscle mass and metabolism.Method: 10 CT and 20 OIS or OIR women were recruited and characterized in CHU Montpellier. All subjects underwent a hyperinsulinemic-euglycemic clamp to determine their glucose infusion rate (GIR). SM biopsies were obtained from the left vastus lateralis. Fresh pieces of muscle were used for analysis of mitochondrial activity, lipids content, proteins synthesis and muscle fiber type and area.Results: In both obese groups, lean mass was elevated and associated with both mTOR pathway activation and increased type 2 fibers area in SM. β-oxidation, glycolysis, mitochondrial activity, and lipid content were equivalent in OIS and OIR SM, while paradoxically, mitochondrial mass and Type 1 fiber content were increased only in OIR SM.Conclusion: Increased lean mass, type I fiber area and mitochondrial content reflect a physiological adaptation in OIR which could allow them maintaining their oxidative capacity and muscle lipid content at the same level than OIS and CT.