Effects of Obesity and Resistance Exercise on the Regulation of Skeletal Muscle Fiber Size

Obesity is the largest health problem in the United States today with an estimated 97 million or 36.5% of the U.S. population being affected. Numerous biochemical and histochemical changes have been reported in obesity. In particular an increase in the skeletal muscle fiber size of obese individuals has been noted. Resistance exercise is known to induce skeletal muscle hypertrophy through the phosphorylation of the Akt/mTOR pathway. The phosphorylation of the Akt/mTOR pathway primarily occurs as a result of the binding of IGF-1 to its receptor on the cell surface. The phosphorylation of Akt/mTOR via IGF-1 occurs at rest and to a greater extent following resistance exercise. Other factors, such as microRNAs may modulate the IGF-1/Akt/ mTOR pathways activity. MicroRNAs are small, non-coding sections of RNA that bind to their target mRNA and prevent translation; thereby, altering gene expression. Understanding how miRNAs modulate skeletal muscle size at rest and following resistance exercise in obese individuals is of great importance for understanding the biochemical and histochemical changes that occur during obesity. Previous studies indicate that an increase in basal activation of the Akt pathway occurs in obese individuals however, the precise mechanisms for this increased activity have not been fully elucidated. Previous studies have also indicated that obese individuals exhibit an impaired response to resistance exercise. It is hypothesized that obese subjects will exhibit increases in the activation of protein synthesis pathways and concurrent changes in the microRNA profile at rest. Following acute resistance exercise, it is hypothesized that obese individuals will exhibit a muted phosphorylation response to resistance exercise. Muscle biopsies were obtained from the vastus lateralis to investigate protein phosphorylation, mRNA and microRNA changes between lean and obese subjects at rest, 15 min and 3 hr. following a bout of resistance exercise. Eight sedentary lean (4 male, 4 female) and eight sedentary obese (4 male, 4 female) individuals participated in the study. Differences were observed in the basal regulation of skeletal muscle mass; reductions in IGF-1 mRNA (LN=1.00, OB=0.53, p\u3c0.05) and increases in miRNA-206 (LN=1, OB=1.55, p\u3c0.05) in obese subjects was noted. A significant negative relationship was observed between miRNA 206 and IGF-1 mRNA at rest (r=-0.54, p\u3c0.05). No difference in the pri-miRNA-206 transcript was found (LN=1, OB=0.99, p\u3e0.05). The results of the present study indicate that obese individuals exhibit a degree of preferential miRNA processing. There were no differences in the signaling response of either the Akt/mTOR, Jak/Stat or Wnt pathways to resistance exercise between lean and obese subjects. The present study suggests that the response to resistance exercise is similar between lean and obese individuals