Kisspeptin a potential therapeutic target in treatment of both metabolic and reproductive dysfunction

Kisspeptins (KPs) are proteins that were first recognized to have antimetastatic action. Later, the critical role of this peptide in the regulation of reproduction was proved. In recent years, evidence has been accumulated supporting a role for KPs in regulating metabolic processes in a sexual dimorphic manner. It has been proposed that KPs regulate metabolism both indirectly via gonadal hormones and/or directly via the kisspeptin receptor in the brain, brown adipose tissue, and pancreas. The aim of the review is to provide both experimental and clinical evidence indicating that KPs are peptides linking metabolism and reproduction. We propose that KPs could be used as a potential target to treat both metabolic and reproductive abnormalities. Thus, we focus on the consequences of disruptions in KPs and their receptors in metabolic conditions such as diabetes, undernutrition, obesity, and reproductive disorders (hypogonadotropic hypogonadism and polycystic ovary syndrome). Data from both animal models and human subjects indicate that alterations in KPs in the case of metabolic imbalance lead also to disruptions in reproductive functions. Changes both in the hypothalamic and peripheral KP systems in animal models of the aforementioned disorders are discussed. Finally, an overview of current clinical studies involving KP in fertility and metabolism show fewer studies on metabolism (15%) and only one to date on both. Presented data indicate a dynamic and emerging field of KP studies as possible therapeutic targets in treatments of both reproductive and metabolic dysfunctions.image HighlightsKisspeptins (KPs) were first discovered to have antimetastatic action. Historically, a role in reproduction was demonstrated. Today, there is growing experimental and clinical evidence that KPs and their receptors regulate metabolism. Disruption of KP and receptor interaction provides an interesting approach to treating metabolic conditions, as well as reproductive disorders. Clinical trials have focused mainly on treating reproductive dysfunctions; however, greater understanding of the biology and mechanisms of action of KPs is being used in the therapeutic armory against insulin-related dysfunctions. Linkage between reproduction and metabolism via the KP system also allows for therapeutic targeting. image