Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System

• DOI: 10.1038/srep11123
• Publication Date: 2015-06-11T14:50:29Z
• Authors: Benjamin J. Weide...; Susan Voong; Fabiola I. Morale...; Michael Z. Kahn; Jonathan Ni; Nicole K. Littlejohn; Kristin E. Claflin; Colin M.L. Burnett; Nicole A. Pearson; Michael L. Lutter; Justin L. Grobe
• Keywords: Male; 2. Zero hunger; 0303 health sciences; Pyridines; Imidazoles; Dietary Fats; Receptor, Angiotensin, Type 2; Article; Losartan; 3. Good health; Renin-Angiotensin System; Mice; 03 medical and health sciences; Intestinal Absorption; Animals; Digestion; Sodium Chloride, Dietary; Gene Deletion

AbstractDietary 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.