Endocrine Abstracts

Background: Metabolic syndrome (MetS) is a clustering of metabolic and cardiovascular risk factors, with insulin resistance being one of the main components. In male, MetS is also associated to hypogonadotropic hypogonadism. Lifestyle modifications (e.g. physical activity) could prevent or considerably reduce MetS progression, however the ability to perform physical activity is often impaired in MetS subjects.

Aim: Considering the known trophic role of T in the increase of muscle mass, this study was aimed at evaluating, in an animal model of MetS, the effects of T treatment on the skeletal muscle composition and function, both in presence or absence of physical exercise.

Methods: Animal model of MetS was obtained by feeding male rabbits, for 12 weeks, with a high fat diet (HFD), with or without T supplementation (30 mg/kg/week), and compared to regular diet animals (control). A subgroup of control, HFD and HFD+T animals was subjected to a treadmill running protocol for 12 weeks.

Results: Gene expression analysis on quadriceps femoris demonstrated a significant reduction of type I muscle fibers markers (oxidative) and an increase of type II muscle fiber markers (glycolytic) in HFD respect to control group. T reverted this effect restoring type I fiber markers and also inducing the expression of mitochondrial respiration chain enzymes and normalizing HFD-induced mitochondrial cristae reduction. Moreover, T treatment increased myogenic and muscle differentiation markers, reduced the atrophy marker Atrogin-1, and restored the HFD-reduced fiber diameter almost to the control level. T ameliorated the expression of genes related to muscle metabolism (insulin-dependent signaling/glucose metabolism), along with insulin resistance, as measured by oral glucose tolerance test (OGTT). At the end of the physical activity protocol, when compared to control rabbits, HFD rabbits showed a significant reduction of physical performance (running distance and running time), while T was able to counteract the HFD-related reduced exercise endurance, also decreasing the lactate production (plateau at T physiological dose, 10.4 nM). Moreover, muscle histology evidenced a further reduction of type-I fibers in HFD as compared to RD and a positive effect of T in maintaining oxidative metabolism and in restoring the mitochondrial cristae arrangement.

Conclusions: Our results indicate that MetS determines a reduced proportion of fatigue-resistant type I fibers in response to physical exercise, while T promotes slow oxidative muscle metabolism thus improving exercise performance. Hence T administration can improve the ability of MetS subjects to perform regular physical activity.