Abstract P067: Sex-Specific Protection Of Fermentable Dietary Fiber On Salt-Sensitive Hypertension And Renal Function

Abstract

Our recent data show that female Dahl Salt-Sensitive (SS) rats are significantly protected from salt-induced hypertension and renal injury and have stark differences in gut microbiota composition compared to males. Gut-derived metabolites are gaining recognition as mechanistic links between the microbiota and disease. One such metabolite is propionate, a protective short-chain fatty acid byproduct of bacterial fiber fermentation. Metabolomics revealed a specific elevation in serum propionate in female versus male SS rats after high salt (HS) (40.3±3.8 vs 24.4±4.2 μM, female vs male, p<0.02, n=6), and propionate administration to male SS rats blunts salt-induced elevations in mean arterial pressure and albuminuria (MAP, HS21: 160.5±6.6 vs 141.8±3.5 mmHg, p<0.05; albuminuria: 437.8±108.6 vs 263.6±50.33 mg/day, p<0.19, control vs propionate, 200mM p.o.; n=3-4). Therefore, the current study hypothesized that substitution of non-fermentable fiber cellulose with the fermentable fiber inulin (AIN-76A, Dyets Inc), a known precursor of short-chain fatty acids, would attenuate salt-sensitivity in males. Males and females were placed on the 0.4% NaCl (LS) inulin diet for one week prior to the switch to a 4.0% NaCl (HS) inulin diet for 4 weeks (inulin-M: n=7, inulin-F: n=6). Controls were maintained on either LS or HS diets containing cellulose (control-M: n=9, control-F: n=11). While there were no significant MAP differences observed in males, the inulin diet significantly reduced albuminuria (370.8±32.4 vs 174.4±30.0 mg/day on HS28, control-M vs inulin-M, p<0.001), reduced CD45+ renal leukocytes (35% reduction, p<0.03), reduced BUN (21.6±2.0 vs 15.4±0.5 mg/dL, p<0.05), and increased creatinine clearance (0.44±0.02 vs 0.55±0.02 ml/min/g KW, p<0.001). In females, inulin significantly lowered MAP (170.2±6.2 vs 154.6±4.5 mmHg on HS28, control-F vs inulin-F, p<0.01), albuminuria (180.3±27.4 vs 68.0±8.3, p<0.001), BUN (21.7±1.2 vs 17.9±0.6 mg/dL, p<0.05), and improved creatinine clearance (0.53±0.04 vs 0.71±0.05 ml/min/g KW, p<0.05). In summary, substitution of the fermentable fiber inulin reduced blood pressure only in females, but all other measures indicate improved renal injury, function, and inflammation in both sexes.