Targeting on Gut Microbial Metabolite Trimethylamine-N-Oxide and Short-Chain Fatty Acid to Prevent Maternal High-Fructose-Diet-Induced Developmental Programming of Hypertension in Adult Male Offspring.

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.

• Authors: Chien-Ning Hsu, Guo-Ping Chang-Chien, Sufan Lin, Chih-Yao Hou, You-Lin Tain
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 63 Issue 18 Pg. e1900073 (09 2019) ISSN: 1613-4133 [Electronic] Germany
• PMID: 31295767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Acetates
• Fatty Acids, Volatile
• Hexanols
• Magnesium Compounds
• Methylamines
• magnesium acetate
• Fructose
• 3,3-dimethylbutan-1-ol
• trimethyloxamine
• trimethylamine

Topics

• Acetates (pharmacology)
• Animals
• Blood Pressure (drug effects)
• Dietary Supplements
• Fatty Acids, Volatile (metabolism)
• Female
• Fructose (adverse effects)
• Gastrointestinal Microbiome (drug effects, genetics)
• Hexanols (pharmacology)
• Hypertension (etiology, prevention & control)
• Magnesium Compounds (pharmacology)
• Male
• Methylamines (metabolism)
• Pregnancy
• Prenatal Exposure Delayed Effects
• Rats, Sprague-Dawley