The renin-angiotensin system in the arcuate nucleus controls resting metabolic rate

Obesity represents the primary challenge to improving cardiovascular health, and suppression of resting metabolic rate (RMR) is implicated in the maintenance of obesity. Increasing evidence supports a major role for the renin-angiotensin system (RAS) within the brain in the control of RMR.

The angiotensin II (ANG) Agtr1a receptor colocalizes with the leptin receptor (Lepr) primarily within cells of the arcuate nucleus (ARC) of the hypothalamus that also express Agouti-related peptide (Agrp). This sub-population of Agtr1a receptors is required for stimulation of thermogenic sympathetic nervous activity and RMR, but not the suppression of food intake or increasing blood pressure, in response to various stimuli including high-fat diet, deoxycorticosterone acetate and salt, and leptin. Agtr1a is localized to a specific subset (SST3) of Agrp neurons within the ARC.

The RAS within the ARC is implicated specifically in RMR control, primarily through Agtr1a localized to the SST3 subset of Agrp neurons. Ongoing research is focused on understanding the unique anatomical projections, neurotransmitter utilization, and signal transduction pathways of Agtr1a within this subset of neurons. Understanding these projections and molecular mechanisms may identify therapeutic targets for RMR and thus obesity, independent of blood pressure and appetite.