Effects evaluation of selective BDNF inhibition on FezF1 and Kiss1 hypothalamic neurons on the regulation of energy metabolism and thermogenesis

Abstract

The energy balance is part of the metabolic homeostasis and is fundamental for the development and survival of organisms. Disorders in energy metabolism are correlated with the development of diseases such as Obesity and Type 2 Diabetes Mellitus. The hypothalamus plays a central role on energy balance control through the production and release of neuropeptides that trigger neural and systemic responses such as hunger control, food intake and stimulation of thermogenesis in brown adipose tissue. BDNF is a neurotrophic factor involved in the promotion and regulation of neurogenesis, and in the differentiation and survival of neurons. Recent studies indicate that BDNF is an important mediator in the process of hypothalamic neurogenesis in response to regulatory signals of energy homeostasis. Data obtained by analysis if single-cell RNAseq from the mapping of the different cell types and their transcripts in the hypothalamus, identified that the hypothalamic neurons that express BDNF are the subpopulations FezF1 and Kiss1. Based on these data, the proposed project aims to inhibit the expression of BDNF specifically in these neuronal populations and to assess the impacts on energy metabolism and thermogenesis induced by brown adipose tissue. (AU)