- Brain Awareness Week
Neural control of cardiovascular and metabolic function
Obesity, a major threat to the health, economy, and general well-being of industrialized nations, is the result of a mismatch between energy intake and output. Essentially every pharmacological therapy for obesity over the last several decades has targeted energy intake behavior or digestive efficiency, and to date all but three drugs have been removed from the market for horrible cardiovascular and neurological side effects. Interestingly, no effective pharmacological therapeutics have been developed to target the energy output side of the energy-balance equation. The renin-angiotensin system (RAS) is a hormone system that exists in the circulation, but also within individual tissues including the kidney, adipose, and brain. RAS-inhibiting drugs are one of the most widely used therapeutics for high blood pressure and cardiovascular diseases. We have determined that the local brain RAS is a major physiological controller of resting metabolic rate. This is meditated through both stimulation of the sympathetic nervous system and suppression of the circulating RAS. Because the activity of the circulating RAS positively correlates with obesity, we hypothesize that the circulating / adipose RAS acts within adipose to suppress basal metabolism, thereby mediating the well-documented link between obesity and hypertension. We hope that leveraging our knowledge of the complex hormonal interactions that control metabolism will lead to the development of novel therapeutics to increase resting metabolic rate. This would represent an entirely new class of therapeutics for obesity, which would act as an adjunct therapy for existing treatments targeting energy intake behavior. Ongoing projects within our lab are therefore targeted at: (1) identifying the receptor(s), second-messenger(s), and effector(s) of RAS actions on adipocytes that suppress metabolic rate, and (2) identifying the mechanisms and sites of action of the RAS within the brain that control blood pressure and metabolic rate.