Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension

Saroj Chakraborty, Sarah Galla, Xi Cheng, Ji Youn Yeo, Blair Mell, Vishal Singh, Beng San Yeoh, Piu Saha, Anna V. Mathew, Matam Vijay-Kumar, Bina Joe

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


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. Chakraborty et al. report a link between dietary salt, a ketone, and experimental hypertension. Intake of a high salt diet lowers the ketone body beta-hydroxybutyrate (βOHB), produced by the liver, which functions to prevent Nlrp3-mediated kidney inflammation. Rescuing βOHB by nutritional supplementation of its precursor attenuates hypertension.

Original languageEnglish (US)
Pages (from-to)677-689.e4
JournalCell Reports
Issue number3
StatePublished - Oct 16 2018

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


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