KNDy neurons and reproductive dysfunctions in animal models of obesity and diabetes

The current obesity and type 2 diabetes epidemic is thought to be largely attributable to excessive consumption of foods and the lack of or very limited physical activity. As obesity and diabetes are widespread throughout the globe, the World Health Organization recognized both diseases among the biggest public health problems. Besides primary metabolic health problems occurring in people with obesity and diabetes, there are numerous secondary problems, including major disruptions of the reproductive system, manifested by disrupted menstrual cycles in women, decreased testosterone levels and spermatogenesis in men, hypogonadism, premature child birth, miscarriages and infertility. However, there is still a fundamental lack of synthetic knowledge considering integration of metabolic and reproductive systems in obese and diabetic patients. Basic research is essential if we are to uncover the mechanisms responsible for metabolic and reproductive failure in cases of obesity and diabetes. Reproduction is influenced by metabolic cues and is governed by the hypothalamic-pituitary-gonadal (HPG) axis and kisspeptin plays an important role in the integration of metabolic and reproductive systems. However, kisspeptin does not act alone to regulate reproduction. A subset of neurons was identified in the arcuate nucleus of the hypothalamus (ARC) that co-localize, in addition to kisspeptin, the neuropeptides, neurokinin B (NKB), and dynorphin (DYN), so called “KNDy neurons”. In this talk recent data on possible mechanisms responsible for disruptions of reproduction in animal models of diet-induced obesity and diabetes will be presented. FINANCIAL SUPPORT: NCN OPUS grant 2015/17/B/ NZ4/02021 .