Energy and glucose homeostasis are regulated by the brain

Dysregulation in neuronal circuits lead to diseases

Body weight is tightly controlled within a species-specific range and organisms have developed a complex regulatory network to avoid either excessive weight gain or chronic weight loss. For energy homeostasis, i.e. maintenance of a stable metabolic state, there must be continual communication between the different organs involved:  adipose tissue, skeletal muscle, liver, pancreas and - the central nervous system (CNS).

The CNS is capable of gathering information on the body’s nutritional state by using feedback signals from peripheral tissues and organs. The neuronal targets of peripheral hormones such as leptin and insulin lay in a structure called hypothalamus. Here, appropriate metabolic and behavioral responses are initiated to change nutritional disposability. These responses cover actions such as the control of eating initiation and cessation, nutrient processing and partitioning of the available energy within different organs and metabolic pathways.

Recent experiments indicate that many of these homeostatic signals modulate the neural circuitry of food reward and motivation. Further evidence suggests that dysregulation in these circuits may play a potential role in the development of obesity and type 2 diabetes mellitus. Though this cross-talk has been intensively studied for many years, we are far from fully understanding how energy balance is maintained.

Our aim is to identify the key neuronal targets of peripheral hormones involved in control of feeding and peripheral glucose metabolism, particularly those of leptin and insulin. We hope to elucidate the intracellular signaling pathways in such neurons as well as the nature of higher integrating neurocircuits orchestrating the multiple outputs associated with nutrient balance and intraorganismal fuel partitioning. Finally, we aim to define the molecular basis of obesity- and aging-associated alterations in these pathways in order to establish novel molecular targets for the treatment of obesity and diabetes.