Abstract
Metabolic syndrome (MetS) clusters cardiovascular and metabolic risk factors, along with hypogonadism (HG) and erectile dysfunction. Lifestyle modifications, including physical exercise (PhyEx), are well-known treatments for this condition. We now report studies on the effect of PhyEx on hypothalamus-pituitary-testis axis and penile relaxation. In this study, we used a non-genomic animal MetS model, previously established in rabbits fed a high fat diet (HFD). Rabbits fed a regular diet (RD) were used as controls. A subset of both groups was trained on a treadmill. In vitro contractility studies were performed to evaluate responsiveness to acetylcholine and electrical field stimulation in corpora cavernosa (CC) strips. Tissue specimens of CC, testis and hypothalamus were obtained at sacrifice and studied by immunohistochemistry and RT-qPCR. HFD rabbits showed typical MetS features including HG (reduced testosterone, T, and LH) and impairment of erectile function. PhyEx in HFD rabbits completely restored plasma T and LH and the penile alterations. At testicular and hypothalamic levels, an HFD-induced inflammatory status was accompanied by reduced T synthesis and GnRH immunopositivity, respectively. In the testis, PhyEx normalized HFD-related macrophage infiltration and pro-inflammatory markers expression, while increasing the expression of steroidogenic enzymes and T synthesis. In the hypothalamus, PhyEx normalized HFD-induced gene expression changes related to inflammation and glucose metabolism, restored GnRH expression, particularly doubling mRNA levels, and regulated expression of molecules related to GnRH release (kisspeptin, dynorphin). Concerning MetS components, PhyEx significantly reduced circulating cholesterol and visceral fat. In multivariate analyses, cholesterol levels resulted the main determinant for MetS-related alterations in penile, testicular and hypothalamic districts.
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