Chien-Ning Hsu1,2, Guo-Ping Chang-Chien3,4, Sufan Lin3,4, Chih-Yao Hou5, You-Lin Tain6,7. 1. Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan. 2. School of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. 3. Center for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung, 833, Taiwan. 4. Super Micro Mass Research and Technology Center, Cheng Shiu University, Kaohsiung, 833, Taiwan. 5. Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung, 811, Taiwan. 6. Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, 833, Taiwan. 7. Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, 833, Taiwan.
Abstract
SCOPE: Alterations of gut metabolites, such as SCFAs and trimethylamine (TMA), and microbial composition are associated with the development of hypertension. Whether maternal 3,3-dimethyl-1-butanol (DMB, an inhibitor for TMA formation) treatment or the predominant SCFA acetate supplementation can prevent programed hypertension induced by a high-fructose diet (HFD) exposure during pregnancy and lactation in adult male offspring is examined. METHODS AND RESULTS: Male offspring are divided into four groups: ND, normal diet; HFD, 60% HFD; ACE, HFD plus 200 mmol L-1 magnesium acetate in drinking water; and DMB: HFD plus 1% DMB in drinking water. Maternal HFD induces programed hypertension in adult male offspring, which is prevented by maternal acetate supplementation or DMB treatment. HFD-induced hypertension is relevant to increased plasma levels of TMA and acetate, and alterations of gut microbial composition. The protective effects of acetate supplementation are associated with decreased plasma TMA level and TMA-to-trimethylamine-N-oxide (TMAO) ratio, and increased renal expression of SCFA receptors. Maternal DMB treatment reduces plasma TMA, TMAO, acetate, and propionate levels. CONCLUSION: Early intervention targeting on gut-microbiota-derived metabolites TMAO and SCFAs to reprogram hypertension may have significant impact to reduce the burden of hypertension.
SCOPE: Alterations of gut metabolites, such as SCFAs and trimethylamine (TMA), and microbial composition are associated with the development of hypertension. Whether maternal 3,3-dimethyl-1-butanol (DMB, an inhibitor for TMA formation) treatment or the predominant SCFA acetate supplementation can prevent programed hypertension induced by a high-fructose diet (HFD) exposure during pregnancy and lactation in adult male offspring is examined. METHODS AND RESULTS: Male offspring are divided into four groups: ND, normal diet; HFD, 60% HFD; ACE, HFD plus 200 mmol L-1 magnesium acetate in drinking water; and DMB: HFD plus 1% DMB in drinking water. Maternal HFD induces programed hypertension in adult male offspring, which is prevented by maternal acetate supplementation or DMB treatment. HFD-induced hypertension is relevant to increased plasma levels of TMA and acetate, and alterations of gut microbial composition. The protective effects of acetate supplementation are associated with decreased plasma TMA level and TMA-to-trimethylamine-N-oxide (TMAO) ratio, and increased renal expression of SCFA receptors. Maternal DMB treatment reduces plasma TMA, TMAO, acetate, and propionate levels. CONCLUSION: Early intervention targeting on gut-microbiota-derived metabolites TMAO and SCFAs to reprogram hypertension may have significant impact to reduce the burden of hypertension.
Authors: Natalia Arias; Silvia Arboleya; Joseph Allison; Aleksandra Kaliszewska; Sara G Higarza; Miguel Gueimonde; Jorge L Arias Journal: Nutrients Date: 2020-08-05 Impact factor: 5.717