Biology

Prof. Herbert Herzog
Neuroscience Division, Garvan Institute of Medical Research, Sydney, AUSTRALIA

Obesity results from the imbalance between energy intake and energy expenditure. While energy intake is mainly determined by food consumption, energy expenditure comprises basal metabolism for sustenance of the organism, physical activity and various bodily functions like digestion of food, as well as thermogenesis for the maintenance of body temperature through heat dissipation. CART is a key neurotransmitter and hormone widely expressed in the hypothalamus suggesting a critical role for CART in appetite control and energy homeostasis. This is supported by findings that CART mRNA levels in the Arc are reduced in response to fasting and that this can be reverted by re-feeding. On the other hand much less is known on CART’s role in controlling energy expenditure. We set out to elucidate the function of CART in energy homeostasis with a focus on the thermoregulatory potential of the peptide using a novel germline CART knockout mouse model. Effects of chronic mild cold exposure at 22 ˚C (RT) were compared with that of the thermoneutral housing at 30 ˚C (TN), where the energy requirement to maintain normal body temperature is suggested to be minimized. The metabolic phenotypes along with the underlying mechanisms were examined and results from that demonstrate that CART is not only a critical regulator of energy expenditure, but also of energy partitioning and utilization.