Abstract

Aging strongly associates with obesity and type 2 diabetes suggesting that the mechanisms controlling body weight and glucose levels deteriorate over time. The cause of obesity is an energy imbalance between calories consumed and calories expended due to the increasingly sedentary lifestyle and the consumption of energy-dense foods. Neuronal circuits exist in the brain governed by specific neurons playing a crucial role in appetite and glucose homeostasis as tight regulation of blood glucose concentration is vital for the survival of the organism. However, many components of these circuits remain unknown. A recent screening identified a novel gene that affects appetite and glucose levels since the suppression of its function in the mouse brain leads to increased food consumption and glucose impairment. Therefore, this gene could play an important role for the development of obesity and type 2 diabetes. In order to test that this proposal aims to first investigate whether this gene is important for feeding and glucose homeostasis over time using genetic tools that have been generated and allow the deletion of this gene in neurons of interests. Secondly, this proposal will explore how this gene works in a neuronal network to control feeding and glucose homeostasis and how its function is influenced by other components of the feeding circuit. The potential impact of this work is to identify a new and important gene in appetite and glucose regulation and a novel pharmacological target for the treatment and prevention of obesity and diabetes that occur due to aging.