Emerging roles for kisspeptin in metabolism

Abstract

Kisspeptin, a neuropeptide hormone, has been firmly established as a key regulator of the hypothalamic-pituitary-gonadal axis and mammalian reproductive behaviour. In recent years, a growing body of evidence has emerged suggesting a role for kisspeptin in regulating metabolic processes. This data suggest that kisspeptin exerts its metabolic effects indirectly via gonadal hormones and/or directly via the kisspeptin receptor in the brain, pancreas and brown adipose tissue. Kisspeptin receptor knockout studies indicate that kisspeptin may play sexually dimorphic roles in the physiological regulation of energy expenditure, food intake and body weight. Some, but not all, in vitro work demonstrates positive effects on glucose-stimulated insulin secretion, which is more marked at higher kisspeptin concentrations. Acute and chronic in vivo rodent, non-human primate and human studies reveal enhancement of glucose-stimulated insulin secretion in response to pharmacological doses of kisspeptin. Although significant progress has been made in elucidating the metabolic effects of kisspeptin, further mechanistic work and translational studies are required to address unanswered questions and establish the metabolic effects of kisspeptin in diverse human populations (including women, people with obesity and people with diabetes).