Central regulation of glucose metabolism Effects of nutrients, serotonin and dopamine

Obesity is a serious health condition, characterized by overconsumption of (calorie dense) nutrients, and is turning into epidemic numbers. Since body weight regulation is orchestrated by the brain, the understanding of the interaction between nutrients and the brain is essential to unravel the pathophysiology underlying the development of obesity. The hypothalamus has been firmly established as a master regulator of glucose homeostasis, and since insulin resistance is a hallmark of the obese condition, studying neuronal circuits in the control of glucose metabolism may provide new therapeutic targets. The overall aim of this thesis was to study the role of nutrients in the central regulation of body weight and peripheral glucose metabolism. To this aim, we studied the effects of nutrients, either derived from a free-choice high-fat high-sugar (fcHFHS) diet or directly infused towards the brain, on nutrient sensing pathways in the hypothalamus and on glucose metabolism. Secondly, we aimed to study a nucleus accumbens-lateral hypothalamus-liver axis in the regulation of glucose metabolism and studied neurotransmitter input from the nucleus accumbens (NAc) to the hypothalamus in relation to glucoregulation.