This study demonstrates that both strength and endurance training improve peripheral insulin sensitivity, whereas only strength training reduces total body fat in HIV-infected patients with lipodystrophy.

In this small randomized controlled trial, we found that improvements in fitness levels correlated with increasing PSADT, suggesting a link between training and disease progression.

Insulin resistance and changes in body composition are side effects of androgen deprivation therapy (ADT) given to prostate cancer patients. The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients. Nine men undergoing ADT for prostate cancer and ten healthy men with normal testosterone levels underwent 12 weeks of endurance training. Primary endpoints were insulin sensitivity (euglycemic-hyperinsulinemic clamps with concomitant glucose-tracer infusion) and body composition (dual-energy X-ray absorptiometry and magnetic resonance imaging). The secondary endpoint was systemic inflammation. Statistical analysis was carried out using two-way ANOVA. Endurance training increased VO 2max (ml(O 2 )/min per kg) by 11 and 13% in the patients and controls respectively (P!0.0001). The patients and controls demonstrated an increase in peripheral tissue insulin sensitivity of 14 and 11% respectively (P!0.05), with no effect on hepatic insulin sensitivity (PZ0.32). Muscle protein content of GLUT4 (SLC2A4) and total AKT (AKT1) was also increased in response to the training (P!0.05 and P!0.01 respectively). Body weight (P!0.0001) and whole-body fat mass (FM) (P!0.01) were reduced, while lean body mass (PZ0.99) was unchanged. Additionally, reductions were observed in abdominal (P!0.01), subcutaneous (P!0.05), and visceral (P!0.01) FM amounts. The concentrations of plasma markers of systemic inflammation were unchanged in response to the training. No group!time interactions were observed, except for thigh intermuscular adipose tissue (IMAT) (PZ0.01), reflecting a significant reduction in the amount of IMAT in the controls (P!0.05) not observed in the patients (PZ0.64). In response to endurance training, ADT-treated prostate cancer patients exhibited improved insulin sensitivity and body composition to a similar degree as eugonadal men. Key Words" prostate cancer " androgen deprivation therapy " endurance training " insulin sensitivity and body composition

Age dependent decline in skeletal muscle function leads to impaired metabolic flexibility in elderly individuals. Physical activity and testosterone treatment have proven efficient strategies for delaying this condition. However, a common molecular pathway has not been identified. Muscle specific miRNAs (myomiRs) regulate metabolic pathways in skeletal muscle, are regulated by physical activity, and have response elements for testosterone in their promoter region. We therefore hypothesized that myomiRs would be regulated in skeletal muscle during aging. We further investigated any potential gender-dependent regulation of these miRNAs. We found that the myomiRs miR-1, miR-133a, and miR-133b were increased in skeletal muscle of elderly men compared to younger men. In addition, miR-133a/133b expression was markedly higher in women compared to men. Elimination of circulating testosterone in men was associated with lower levels of miR-133a and miR-133b. A positive regulatory effect of testosterone on miR-133a/133b expression was confirmed in castrated male C57BL/6J mice and in a model of primary human myocytes. Yet, an improvement of fitness level in the testosterone depleted men resulted in a down-regulation of miR133a/b. In conclusion, alterations in fitness level and circulating testosterone seem to represent two independent regulatory events where testosterone is a specific regulator of miR-133a/b expression.