Energy Homeostasis and Kisspeptin System, Roles of Exercise and Outcomes with a Focus on Male Reproductive Health

Background: Obesity is a multisystemic health problem causing chronic diseases like diabetesor cardiovascular diseases, but also reproductive dysfunctions like infertility in adultsor altered puberty onset in children. Exercise is a recognized intervention to control or preventenergy imbalance, thus deeply contributing to metabolic health in physiological andpathological conditions. The kisspeptin system (KS), the main gatekeeper of reproductionand puberty onset in mammals, is also an upcoming “metabolic sensor”, linking energyhomeostasis to reproductive ability both centrally and peripherally. Objectives: This narrativereview aims at summarizing recent evidence from animal models and human studieson the role of the KS in energy homeostasis, with a focus on the upcoming role of the KS asa metabolic sensor able to modulate the functionality of the hypothalamus–pituitary–gonadaxis in males as an adaptive response to exercise. Methods: PubMed and Scopus search(date: 2015–2025; keywords: kisspeptin and metabolism, male reproduction or exercise;kisspeptin and doping). Results and Conclusions: This review article illustrates the crucialrole of the KS in linking energy homeostasis and male reproduction at the central andperipheral levels, and modulation of the KS by exercise in physiological and pathologicalconditions. Due to the large amount of data from animal models, knowledge gaps occurin the analysis of the relationship among KS, energy homeostasis, male reproduction andexercise in humans, particularly in the case of overtraining. Lastly, kisspeptin inclusion inthe doping list is also discussed.