TY - JOUR
T1 - Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension
AU - Chakraborty, Saroj
AU - Galla, Sarah
AU - Cheng, Xi
AU - Yeo, Ji Youn
AU - Mell, Blair
AU - Singh, Vishal
AU - Yeoh, Beng San
AU - Saha, Piu
AU - Mathew, Anna V.
AU - Vijay-Kumar, Matam
AU - Joe, Bina
N1 - Funding Information:
All authors thank Dr. John P. Rapp, Emeritus Professor, University of Toledo, for blinded scoring of renal injury and Mr. Sifaat Muhtasham, Ms. Naveena Luke, and Mr. Anay Hindupur for technical assistance. This work was supported by institutional funding from the University of Toledo College of Medicine to the University of Toledo Microbiome Consortium. A.M. acknowledges support from the National Heart, Lung, and Blood Institute ( K08HL130944 ). M.V.-K. acknowledges funding from NIH ( RO1 CA219144 ). V.S. and P.S. are funded by fellowships from the Crohn's and Colitis Foundation of America (CCFA).
Funding Information:
All authors thank Dr. John P. Rapp, Emeritus Professor, University of Toledo, for blinded scoring of renal injury and Mr. Sifaat Muhtasham, Ms. Naveena Luke, and Mr. Anay Hindupur for technical assistance. This work was supported by institutional funding from the University of Toledo College of Medicine to the University of Toledo Microbiome Consortium. A.M. acknowledges support from the National Heart, Lung, and Blood Institute (K08HL130944). M.V.-K. acknowledges funding from NIH (RO1 CA219144). V.S. and P.S. are funded by fellowships from the Crohn's and Colitis Foundation of America (CCFA).
Publisher Copyright:
© 2018 The Author(s)
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/10/16
Y1 - 2018/10/16
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2018.09.058
DO - 10.1016/j.celrep.2018.09.058
M3 - Article
C2 - 30332647
AN - SCOPUS:85054711695
VL - 25
SP - 677-689.e4
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 3
ER -