Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis

The tight coordinated regulation of food intake and energy expenditure represents a prerequisite for stable body weight control. The central nervous system receives information from the periphery of the body about the fuel sources available either via hormonal signals such as leptin and insulin as well as directly by nutrient components such as amino acids, glucose and fatty acids. This allows for appropriate adaptation of food intake, energy expenditure, locomotor activity, as well as peripheral glucose metabolism. Anatomical lesion experiments, pharmacological inhibition of signaling pathways and, more recently, the analysis of conditional mouse mutants with modifications of hormone and nutrient signaling in defined neuronal populations have broadened our understanding of how these complex neurocircuits interact and how their activity is regulated. Although the hypothalamus integrates various hormonal and neuronal signals to regulate appetite and metabolism, additional neuronal circuits can influence and eventually override this system. One such system comprises mid-brain dopamine neurons, which play a pivotal role in reward behavior and the motivational aspects of feeding behavior. To define the role of insulin signal transduction in dopaminergic mid-brain neurons of mice, we have inactivated the insulin receptor specifically in these cells. The presentation will focus on the genetic analysis of interacting neurocircuits involved in these processes.