Adipose Tissue Dysfunction and Obesity-Related Male Hypogonadism

Abstract

Obesity is a chronic illness associated with several metabolic derangements and comorbidities (i.e., insulin resistance, leptin resistance, diabetes, etc.) and often leads to impaired testicular function and male subfertility. Several mechanisms may indeed negatively affect the hypothalamic-pituitary-gonadal health, such as higher testosterone conversion to estradiol by aromatase activity in the adipose tissue, increased ROS production, and the release of several endocrine molecules affecting the hypothalamus-pituitary-testis axis by both direct and indirect mechanisms. In addition, androgen deficiency could further accelerate adipose tissue expansion and therefore exacerbate obesity, which in turn enhances hypogonadism, thus inducing a vicious cycle. Based on these considerations, we propose an overview on the relationship of adipose tissue dysfunction and male hypogonadism, highlighting the main biological pathways involved and the current therapeutic options to counteract this condition.

Keywords: adipose tissue; hypogonadism; infertility; obesity; reproductive dysfunction.

Figure 1

The vicious cycle of obesity–hypogonadism. Obesity-induced AT dysfunction impaired the secretion of several mediators affecting the release of GnRH from the hypothalamus as well as of FSH and LH from the pituitary gland. Low levels of these hormones worsen testicular function in terms of the reduction of testosterone production, leading to overt hypogonadism. The decrease in testosterone levels further exacerbates the impairment of AT in terms of a decreased rate of lipolysis and increased lipogenesis, the extent of which accelerates the failure of HPT axis, thus sustaining a feedforward detrimental loop. Abbreviations: adiponectin receptor (AdipoR); follicle-stimulating hormone (FSH); gonadotropin-releasing hormone (GnRH); interleukin-1β (IL-1β); interleukin-6 (IL-6); suppressor of cytokine signaling 3 (SOCS3); tumor necrosis factor α (TNFα); leptin receptor (LEPR); luteinizing hormone (LH); LH receptor (LHR); phosphorylated Janus kinase 2 (pJAK2); reactive oxygen species (ROS); steroidogenic acute regulatory protein (STAR); signal transducer and activator of transcriptor 3 (STAT3).