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Merck

Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension.

Cell reports (2018-10-18)
Saroj Chakraborty, Sarah Galla, Xi Cheng, Ji-Youn Yeo, Blair Mell, Vishal Singh, BengSan Yeoh, Piu Saha, Anna V Mathew, Matam Vijay-Kumar, Bina Joe
要旨

Dietary salt reduction and exercise are lifestyle modifications for salt-sensitive hypertensives. While exercise has prominent metabolic effects, salt has an adverse effect on metabolic syndrome, of which hypertension is a hallmark. We hypothesized that dietary salt impacts metabolism in a salt-sensitive model of hypertension. An untargeted metabolomic approach demonstrates lower circulating levels of the ketone body, beta-hydroxybutyrate (βOHB), in high salt-fed hypertensive rats. Despite the high salt intake, specific rescue of βOHB levels by nutritional supplementation of its precursor, 1,3-butanediol, attenuates hypertension and protects kidney function. This beneficial effect of βOHB was likely independent of gut-microbiotal and Th17-mediated effects of salt and instead facilitated by βOHB inhibiting the renal Nlrp3 inflammasome. The juxtaposed effects of dietary salt and exercise on salt-sensitive hypertension, which decrease and increase βOHB respectively, indicate that nutritional supplementation of a precursor of βOHB provides a similar benefit to salt-sensitive hypertension as exercise.

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Sigma-Aldrich
フルオレセインイソチオシアナート–デキストラン, average mol wt 3,000-5,000
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リポポリサッカリド 大腸菌0128:B12由来, purified by gel-filtration chromatography
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Sigma-Aldrich
(±)-1,3-ブタンジオール, ReagentPlus®, 99.5%
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