High Intensity Interval Training Changes Skeletal Muscle Insulin Signalling Pathway Of Obese Individuals

Abstract

PURPOSE: Obesity, characterized as excess of body fat (BMI ≥ 30 kg•m-2), is related to the development of various metabolic disorders, including insulin resistance. Exercise is known to serve as a non-pharmacological approach to increase skeletal muscle insulin sensitivity, although the mechanisms have not been fully elucidated. Additionally, the molecular underpinnings of the effects of high intensity interval training (HIIT) on insulin resistance are less understood. This study evaluated the effects of HIIT on biochemical and molecular markers related to insulin resistance in physically inactive obese individuals. METHODS: 9 obese insulin sensitive (OB; 32 ± 10 y; 92.4 ± 12.9 kg; 35.1 ± 3.8 kg•m-2) and 8 obese insulin resistant (OBR; 30 ± 11 y; 106.0 ± 19.6 kg; 37.8 ± 4.6 kg•m-2) volunteers were subjected to 8 weeks of HIIT using a cycle ergometer. Insulin resistance was defined as homeostasis model assessment index (HOMA-IR) equal or greater than 2.71. Before and after the training, a maximal ramp test was performed to measure maximal cycling power output. HIIT was performed 3 times a week with progressively increasing intensity and volume (8 to 12 bouts of 1 min duration at 80 to 110% of the maximum power output separated by 1 min active recovery at 30 W). A muscle biopsy and venous blood were performed 72 hours before and after HIIT to allow HOMA-IR calculation. Skeletal muscle samples were analyzed by Western Blot. RESULTS: HIIT increased insulin sensitivity evaluated by HOMA-IR in OBR (4.4 ± 1.4 versus 4.1 ± 2.2, p=0.02) but not in OB (1.8 ± 0.5 versus 2.3 ± 1.0) volunteers. In skeletal muscle, HIIT increased phosphorylation of the insulin receptor substrate (Tyr612), Protein kinase B (AKT Ser473) and protein kinase dependent calcium/calmodulin (CaMKII) (Thr286), and increased expression of β-hydroxyacyl-CoA dehydrogenase (β-HAD), and cytochrome C oxidase (COX-IV). There was also a reduction of phosphorylation of extracellular signal regulated kinase (ERK1/2) in OBR. CONCLUSIONS: 8 weeks of HIIT promoted improvements in insulin sensitivity, modified components of insulin signaling pathway, and improved oxidative metabolism in skeletal muscle. These changes were independent of changes in body fat. This work was supported by CAPES (PNPD-2455/2011), FAPEMIG (CDS APQ01621-10), and CNPq (477154/2011-5) grants.