We pursue multi-pronged investigations into how energy availability is sensed, communicated and integrated. We study how fat tissue senses lipid stores and communicates this information to neural circuits, which integrate physiological inputs, to regulate organismal behavior. Using a confluence of cutting-edge techniques in the model organism the fruit fly, Drosophila melanogaster, we adopt a multi-scale approach. The goal is to illuminate fundamental mechanisms governing energy homeostasis, with particular focus on dissecting how chronic nutrient surplus disrupts energy balance.
During evolution, with nutrient scarcity as the selection pressure, conserved homeostatic mechanisms developed to be highly sensitive to even a small a decrease in available nutrients. When food was plentiful the excess energy is stored as fat reserves, which can be mobilized during a future scarcity. In most developed nations it is nutrient surplus, not scarcity, which is the prevalent state. Our ancestors were not selected to counter a state of perpetual ‘over-nutrition’. Absence of appropriate surplus-coping mechanisms causes improper energy storage resulting in obesity. Physiological and psychological outcome of nutrient surplus underlies diseases such as diabetes, anorexia, bulimia and lipodystrophies. Moreover, disorders of metabolism have profound effects on progression of cancer and neurodegeneration.
In the past, most investigations have focused on how cells respond to nutritional scarcity. This resulted in elucidation of cellular nutrient scarcity mechanisms, in great detail and with high precision. However, we have a less clearly defined understanding of how organisms sense nutrient surplus, and adapt to chronic over-nutrition. Hence, it is crucial to investigate how surplus signaling mechanisms work, and why they fail. Working out the chronic nutritional surplus signaling network will serve up targets for pharmaceutical interventions to mitigate obesity.