Common Laboratory Chow Diets Differentially Affect Energy Homeostasis and Modify Metabolic and Electrolyte Balance Effects of DOCA‐salt in Wildtype Mice

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Roughly 27% of humans with essential hypertension (HTN) exhibit low circulating renin, and this condition is experimentally modeled by subcutaneous administration of deoxycorticosterone acetate (DOCA) and high dietary sodium (the DOCA‐salt model). The quantitative effects of DOCA‐salt upon blood pressure, renal function, and energy homeostasis differ in literature reports, due to methodological differences including varied use of uninephrectomy or limiting animals to only saline drinks, with or without potassium supplementation. Here, we examined the hypothesis that the effects of DOCA‐salt on metabolic and electrolyte endpoints would be modified by diet. Male C57BL/6J mice (Jackson Labs; weaned onto LabDiet 5K52) arrived at 6 weeks of age and were immediately randomly placed onto either LabDiet 5L0D (24.1% protein, 5.2% fiber, 0.17 mEq Na/g, 2.89 kcal/g), Teklad 2920 (19.1% protein, 2.7% fiber, 0.043 mEq Na/g, 3.10 kcal/g), or Teklad 7913 (18.0% protein, 4.0% fiber, 0.130 mEq Na/g, 3.10 kcal/g), and offered autoclaved, deionized water to drink in single‐housing conditions (n=16 each). After 3 weeks, body mass differed by diet (5L0D: 3.13±0.31, 2920: 3.61±0.28, 7913: 2.48±0.16 g (mean±sem); p<0.05 by ANOVA) despite the observation that total daily caloric absorption rates (by bomb calorimetry) were similar across groups (14.6±0.3, 14.9±0.6, 14.7±0.2 kcal/d). Mice then underwent sham surgery and were maintained on assigned chow and water (n=8/diet), or were implanted with a subcutaneous 50 mg pellet of DOCA (Sigma) and offered 0.15 M NaCl drink in addition to assigned chow and water (n=8/diet). Expected major effects of DOCA‐salt (eg – to increase Na & fluid intake, urine volume, plasma Na & BUN, and renal mass while decreasing plasma K & Cl, all p<0.05) were observed in all diet groups. As hypothesized, diet significantly modified many effects of 3 weeks of DOCA‐salt (2‐way ANOVA, followed by Sidak multiple‐comparisons procedure), including: body mass (decreased (p<0.05) with DOCA‐salt on 5L0D, vs no change on 2920 or 7913), adipose masses (eg; interscapular “brown” fat mass increased (p<0.05) with DOCA‐salt on 7913, vs no change on 5L0D or 2920), total daily Na intake and urine volume (larger increases with DOCA‐salt on 5L0D vs 5L0D or 2920). We conclude that various common laboratory chow diets have significantly different effects upon aspects of energy balance and electrolyte homeostasis, and that maintenance on these different diets can quantitatively modify the effects of DOCA‐salt in mice.Support or Funding InformationHL134850, HL084207