MO099REPROGRAMMING HYPERTENSION PROGRAMMED BY HIGH-FAT DIET: THE ROLE OF GARLIC OIL

Abstract

Abstract Background and Aims Perinatal high-fat (HF) diet programs high blood pressure (BP) in adult offspring. Hydrogen sulfide (H2S) has shown benefits in hypertension by restoration of nitric oxide (NO) bioavailability and alterations of gut microbiota. Garlic, a naturally dietary source of H2S donors, supplementation has shown benefits in hypertension. We aimed to examine whether maternal garlic oil supplementation can prevent hypertension programmed by maternal and post-weaning high-fat diet in adult offspring and whether its protective effects are related to mediation of H2S-genetaing system, alterations of gut microbiota composition, and microbiota metabolite short chain fatty acids (SCFAs). Method Pregnant rats received either a normal diet (ND) or HF diet (D12331, Research Diets, Inc.) Garlic oil (GO) or vesicle was administered daily by oral gavage at 100 mg/kg/day during pregnancy and lactation. Male offspring were weaned at 3 weeks of age, and onto either ND or HF diet to 16 weeks of age. Male offspring were assigned to four groups (n=8/group): ND, HF, ND+GO, and HF+GO. Garlic supplementation during pregnancy and lactation protected against programmed hypertension in adult male offspring fed with HF diet. All offspring were killed at 16 weeks of age. NO-related parameters were analyzed by HPLC. Plasma levels of SCFA were determined using GC-MS method. Fecal microbial community was analyzed using a combination of 16S rRNA gene and fecal metagenome sequence analysis. Results Garlic supplementation during pregnancy and lactation protected against programmed hypertension in adult male offspring fed with HF diet. Garlic oil supplementation caused a significant increase in plasma levels of acetate, propionate, and butyrate. NO bioavailability was augmented by garlic oil supplementation, represented by decreases of plasma levels of asymmetric and symmetric dimethylarginine (ADMA and SDMA) levels, and increased plasma L-arginine-to-ADMA ratio (AAR). HF intake associated with decreased α-diversity was quantified by Shannon diversity index. The Analysis of similarities (ANOSIM) demonstrated the difference in the gut microbiota among the four groups existed (All p < 0.05), indicating that four groups had distinct enterotypes. Additionally, garlic oil supplementation increased abundance of genus Lactobacillus, but decreased genera Turicibacter and Staphylococcus. Moreover, the linear discriminant analysis effect size (LEfSe) algorithm analysis identified several microbial markers including genera Lactobacillus, Staphylococcus, and Turicibacter. Conclusion The beneficial effects of garlic oil were associated with increased renal mRNA expression and activity of H2S-generating enzymes, increased NO bioavailability, increased plasma SCFA levels, and alterations of gut microbiota composition. Our data revealed associations between H2S-generating pathway in the gut and kidneys, NO system, gut microbiota, and microbiota-derived metabolites in hypertension programmed by HF intake and provided insight to garlic oil as a hypertension reprogramming strategy for further translational research.