During the recent decades, we have witnessed fertility rates dwindling worldwide, while metabolic diseases followed an opposite tendency, with their prevalence dramatically increasing [1][2][3]. Those trends are particularly marked in both developed and under-development countries, where type 2 diabetes mellitus (T2DM) and obesity are key players in the ever-increasingly number of new metabolic disorder cases, fostered by overeating and sedentarism [3,4].The previous premises, acting during the same time period, arose the possibility of metabolic disorders and infertility were somehow connected. In addition, a normal reproductive function requires a significant quantity of energy, so it is highly influenced by energy homeostasis [5,6]. Furthermore, the prevalence of reproductive dysfunction is significantly higher in people suffering from metabolic diseases, particularly males. From all the infertility cases documented worldwide, about a third account for male-only factor. In fact, even a pre-diabetic state is enough to harm sperm parameters [7]. However, the mechanisms underlying this link are still controversial.The most evident burdens of metabolic diseases on male reproductive function are caused by complications on other systems. Obese men experience more cases of erectile dysfunction than lean males, due to cardiovascular co-morbidities. They can also suffer coitus difficulties due to excessive pubic fat deposition, which leads to other reproductive health risks, such as scrotal heating, responsible for defects in spermatogenesis. T2DM patients are also prone to erectile dysfunction and scrotal heating due to vascular disease [8]. Nevertheless, the most severe and persistent effects of metabolic disorders on male reproductive function are linked to hormonal impairment.The steroidogenic potential of adipocytes is a good example of how a metabolic disorder, in this case obesity, is able to induce hormonal problems, and consequently affect reproductive function. Adipocytes have intense p450 aromatase, an enzyme responsible to convert testosterone into 17β-oestradiol (E 2 ). Thus, obese men present higher E 2 bloodstream concentration and lower testosterone than lean men. This action results in two immediate negative effects for male fertility: 1) Testosterone depletion leads men towards an hypogonadal state, and 2) E 2 secretion may exert negative feedback over pituitary gland and thus disrupt the reproductive axis. The former, inhibits the release of Gonadotrophin-Releasing Hormone (GnRH) and, consequently, of the gonadotrophins Follicle Stimulatory-Hormone (FSH) and Luteinizing Hormone (LH). LH stimulates testosterone release from Leydig Cells, so ultimately reproductive axis disruption leads to the formerly mentioned lower testosterone concentration. Sertoli cells are crucial for spermatogenesis because they establish the blood-testis barrier (BTB), one of the tightest blood-barriers of our body [8]. Testosterone (and their precursors) and FSH direct Sertoli cell metabolism towards a glycolytic profile, up...