Dietary fats and sodium are both palatable and are hypothesized to synergistically contribute to ingestive behavior and thereby obesity. Contrary to this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary sodium content. This suppressive effect of dietary sodium upon weight gain was mediated specifically through a reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism. Replacement of circulating angiotensin II levels reversed the effects of high dietary sodium to suppress digestive efficiency. While the AT1 receptor antagonist losartan had no effect in mice fed low sodium, the AT2 receptor antagonist PD-123,319 suppressed digestive efficiency. Correspondingly, genetic deletion of the AT2 receptor in FVB/NCrl mice resulted in suppressed digestive efficiency even on a standard chow diet. Together these data underscore the importance of digestive efficiency in the pathogenesis of obesity, and implicate dietary sodium, the renin-angiotensin system, and the AT2 receptor in the control of digestive efficiency regardless of mouse strain or macronutrient composition of the diet. These findings highlight the need for greater understanding of nutrient absorption control physiology, and prompt more uniform assessment of digestive efficiency in animal studies of energy balance.

Through its actions at the AT1A receptor in the hypothalamus, the renin‐angiotensin system contributes to the control of resting metabolic rate and blood pressure. Activation of microglia is required for angiotensin‐dependent hypertension, and exposure to high fat diet increases microglia infiltration in the hypothalamus. We therefore hypothesized that angiotensin AT1A receptors are expressed on microglia within the hypothalamus, and that these cells may play a role in the development of obesity‐hypertension. Brains from mice expressing green fluorescent protein via the angiotensin AT1A promoter (“NZ44” mice from the GenSat Project) were sectioned and immunostained to label microglia via antibodies against allograft inflammatory factor 1 (IBA1) conjugated to red fluorescent protein. When mice were maintained on standard chow diet, we observed dual‐fluorescent cells within the ventromedial hypothalamus, but not in the arcuate nucleus, median eminence, paraventricular nucleus, dorsomedial hypothalamus, or subfornical organ despite substantial numbers of singly‐fluorescent cells in each of these regions. Together, these data support a region‐specific expression of AT1A in microglia. Ongoing studies are focused on investigating the effects of dietary interventions (e.g. – high fat diet) and hypertensive stimuli (e.g. – deoxycorticosterone acetate (DOCA)‐salt treatment) upon region‐specific microglial infiltration, activation, and expression of AT1A.