Physical activity counteracts metabolic syndrome-induced hypogonadotropic hypogonadism and erectile dysfunction in the rabbit

Abstract

Metabolic syndrome (MetS) clusters cardiovascular and metabolic risk factors along with hypogonadism and erectile dysfunction. Lifestyle modifications including physical exercise (PhyEx) are well-known treatments for this condition. In this study, we analyzed the effect of PhyEx on hypothalamic-pituitary-testis axis and erectile function by use of an 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. HFD rabbits showed typical MetS features, including HG (reduced 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 gonadotropin-releasing hormone (GnRH) immunopositivity, respectively. In the testis, PhyEx normalized HFD-related macrophage infiltration and increased 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 as the main factor associated with MetS-related alterations in penile, testicular, and hypothalamic districts. In conclusion, our results show that PhyEx may rescue erectile function, exert anti-inflammatory effects on hypothalamus and testis, and increase LH levels and T production, thus supporting a primary role for lifestyle modification to combat MetS-associated hypogonadism and erectile dysfunction.

Testosterone improves muscle fiber asset and exercise performance in a metabolic syndrome model

“…Interestingly, we recently demonstrated that, when HFD rabbits were trained with aerobic physical activity on a treadmill, they exhibited a reversal of the hypogonadotropic condition, including a restoration of the hypothalamic network controlling GnRH production. However, these animals also showed a deficient muscular response to fatigue, as demonstrated by a significant reduction of both running distance and running time in comparison to the control group fed a regular diet (Morelli et al 2019). Hence, they are less prone to perform physical exercise.…”

“…; RD + testosterone group, n = 8) for 12 weeks. A subset of rabbits for each group (RD, n = 10; HFD, n = 12; HFD + testosterone, n = 10; RD + testosterone n = 4) was trained with a physical exercise (PhyEx) running protocol on a treadmill with increasing intensity, duration and frequency during the 12 weeks, as previously published (Morelli et al 2019) and described below. The remaining animals were left in the cages for the same period.…”

“…PhyEx rabbits were killed 90 min after the end of the exercise. Blood samples for glucose, total cholesterol, triglycerides, LH and testosterone measurements were collected as previously described (Morelli et al 2019). In particular, for the PhyEx rabbits, blood samples were obtained immediately before (pre-exercise), immediately after (end exercise) and 90 min after the end (recovery) of the last exercise at week 12 for measuring blood lactate concentration, testosterone, LH, glucose and triglycerides.…”

“…In particular, for the PhyEx rabbits, blood samples were obtained immediately before (pre-exercise), immediately after (end exercise) and 90 min after the end (recovery) of the last exercise at week 12 for measuring blood lactate concentration, testosterone, LH, glucose and triglycerides. Mean arterial blood pressure (MAP) was measured and afterward, the rabbits were killed by a lethal dose of pentobarbital (Morelli et al 2019). After killing, the vastus medialis muscle was rapidly dissected and appropriately stored for the subsequent analyses.…”

“…Plasma cholesterol, triglycerides and glucose levels were measured by using an automated system (ADVIA 2004 Siemens Chemistry System; Siemens Science Medical Solution Diagnostic), as previously described (Filippi et al 2009). Plasma testosterone and LH levels were measured using a chemiluminescence system (Immunolite 2000 Siemens, Siemens Healthcare Diagnostics) and an ELISA kit (Repropharm Vet, Nouzilly, France), respectively, as previously described (Morelli et al 2019).…”