title: Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System.
abstract: 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.
authors.affiliation: Departments of Pharmacology, University of Iowa, Iowa City, IA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Weidemann
authors.affiliation: Departments of Pharmacology, University of Iowa, Iowa City, IA.
authors.forename: Susan
authors.initials: S
authors.lastname: Voong
authors.affiliation: Departments of Pharmacology, University of Iowa, Iowa City, IA.
authors.forename: Fabiola I
authors.initials: FI
authors.lastname: Morales-Santiago
authors.affiliation: Departments of Psychiatry, University of Iowa, Iowa City, IA.
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Kahn
authors.affiliation: Departments of Pharmacology, University of Iowa, Iowa City, IA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ni
authors.affiliation: Departments of Pharmacology, University of Iowa, Iowa City, IA.
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Littlejohn
authors.affiliation: Departments of Pharmacology, University of Iowa, Iowa City, IA.
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Claflin
authors.affiliation: Departments of Pharmacology, University of Iowa, Iowa City, IA.
authors.forename: Colin M L
authors.initials: CM
authors.lastname: Burnett
authors.affiliation: Departments of Pharmacology, University of Iowa, Iowa City, IA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Pearson
authors.affiliation: 1] Departments of Psychiatry, University of Iowa, Iowa City, IA. [2] The Fraternal Order of Eagles' Diabetes Research Center, University of Iowa, Iowa City, IA. [3] The Obesity Research and Education Initiative, University of Iowa, Iowa City, IA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Lutter
authors.affiliation: 1] Departments of Pharmacology, University of Iowa, Iowa City, IA. [2] The Fraternal Order of Eagles' Diabetes Research Center, University of Iowa, Iowa City, IA. [3] The Obesity Research and Education Initiative, University of Iowa, Iowa City, IA. [4] The Center for Hypertension Research, University of Iowa, Iowa City, IA.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Grobe
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000378:metabolism / Q000494:pharmacology*; D004063:Digestion / Q000187:drug effects* / Q000235:genetics; D017353:Gene Deletion; D007093:Imidazoles / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects / Q000235:genetics; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D011725:Pyridines / Q000494:pharmacology; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*
chemical_list: D004041:Dietary Fats; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D017673:Sodium Chloride, Dietary; C073402:PD 123319; D019808:Losartan