PO-01-049 Testosterone counteracts metabolic syndrome-related changes in skeletal muscle fiber metabolism and improves exercise performance in the rabbit

Abstract

Lifestyle modifications, including physical exercise (PhyEx) are well-known treatments for metabolic syndrome (MetS), a cluster of metabolic and cardiovascular risk factors often associated to hypogonadism. Given the trophic role of testosterone (T) on skeletal muscle (SkM) mass, this study was aimed at evaluating the effects of T treatment on SkM metabolism and exercise performance in male rabbits with high fat diet (HFD)-induced MetS. HFD rabbits, treated or not with T (HFD+T; 30 mg/kg/week) for 12 weeks were compared to regular diet animals (RD). A subset of each group were exercise-trained on a treadmill for 12 weeks. SkM samples were collected for subsequent analyses. HFD determined an increased gene expression of type-II (fast, glycolytic) and a significant decrease of type-I (slow, oxidative) muscle fiber markers, as compared to RD group. T reverted these effects, also inducing the expression of mitochondrial respiration chain enzymes and normalizing HFD-induced mitochondrial cristae reduction. Fiber typing by PAS-staining in SkM cross-sections confirmed a shift from type-I to type-II fibers in HFD, which was normalized by T. Moreover, T significantly increased the expression of both myogenic and muscle metabolism (insulin-dependent signaling, lipid turnover) markers. Preliminary Results in rabbit SkM satellite cells confirmed the positive effect of T on myogenesis. At the end of the PhyEx protocol, when compared to RD, HFD rabbits showed a significant reduction of both running distance and running time, while T counteracted this effect, also decreasing the lactate production. Muscle histology evidenced a further reduction of type-I fibers in HFD compared to RD and the positive effect of T in maintaining oxidative metabolism, as also demonstrated by mitochondrial ultrastructure analysis.