Abstract Body: Agouti-related peptide (AgRP) neurons in the hypothalamic arcuate nucleus (ARC) control feeding and resting metabolic rate (RMR) and may also contribute to blood pressure (BP) and heart rate (HR) control. Our recent studies demonstrate that three subtypes of ARC AgRP neurons can be distinguished by differential expression of angiotensin II (ANG) receptors and differential electrophysiological responses to ANG. The "Type 1" subtype of AgRP neurons in the ARC express the ANG type 1 receptor (AT₁R), and application of ANG inhibits these cells via a Gi cascade, ultimately causing increased RMR. Other published data suggest that AT₁R action in AgRP neurons may also stimulate BP. Thus, we hypothesized that cell-specific ablation of Type 1 AgRP neurons would disinhibit (increase) RMR and BP. Within the ARC, only Type 1 AgRP neurons express AT₁R. Thus, cell-specific ablation of Type 1 AgRP neurons was achieved by injecting an Adeno-associated virus (AAV) encoding Cre-activatable Caspase3 into the ARC of adult AT₁R^CRE mice that express Cre-recombinase via the AT₁R locus (n=10m+6f). Cre-deficient mice receiving AAV-Casp3 injection, mice receiving anesthesia but no virus, and AT₁R^CRE mice receiving an AAV vector encoding GFP were used as controls (n=21m+10f). Multiplexed metabolic phenotyping demonstrated that two weeks after injection, ablation of Type 1 cells grossly stimulated RMR (+11%: 0.331±0.007 vs. 0.366±0.008 kcal/h, p<0.01) without affecting activity-dependent expenditure; and paradoxically increased meal initiations (+10%, p<0.05) but reduced meal size (-14%, p<0.05), yielding no net change in total food intake after correction for body size and composition (+7%, p=0.24). Ablation of Type 1 neurons also increased preferred ambient temperature in a thermal gradient (29.4±0.3 vs 30.9±0.1 °C, p<0.01). In a separate cohort instrumented with radiotelemetric BP transducers (n=6m), HR progressively decreased (24h avg: -58±9 bpm, p<0.01) as systolic BP tended toward an increase (24h avg: +6±3 mmHg, p=0.10) through 5-7 weeks after ablation. We conclude that AT₁R-expressing AgRP Type 1 neurons critically contribute to RMR control and appear to also influence BP/HR and feeding control. Therefore, we posit that altered function of these cells may mechanistically contribute to changes in RMR, BP/HR, and feeding control associated with obesity.