Evidence map›Paper›PMID 40726393›Full record

ArticleHypertension (Dallas, Tex. : 1979)2025

Epigenetic Histone β-Hydroxybutyrylation Contributes to Renoprotection by β-Hydroxybutyrate in the Dahl Rat.

Juthika Mandal, Sachin Aryal, Ishan Manandhar, Saroj Chakraborty, Xue Mei, Beng San Yeoh, Blair Mell, Andrew Kleinhenz, Ramakumar Tummala, Tao Yang and 6 more

Abstract read
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Food as Medicine for Hypertension: Microbiota as Mediators.Hypertension (Dallas, Tex. : 1979) · 2025
    Review
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Juthika Mandal *Center for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).
Sachin Aryal *Center for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).ORCID 0000-0002-1939-6338
Ishan Manandhar *Center for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).ORCID 0000-0001-6772-2540
Saroj ChakrabortyCenter for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).ORCID 0000-0002-8728-8187
Xue MeiCenter for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).
Beng San YeohCenter for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).ORCID 0000-0002-7723-8733
Blair MellCenter for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).
Andrew KleinhenzDepartment of Pathology, University of Toledo College of Medicine and Life Sciences, OH (A.K., W.T.G.).
Ramakumar TummalaCenter for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).ORCID 0000-0002-3887-3566
Tao YangCenter for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).ORCID 0000-0002-4182-9793
Piu SahaCenter for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).
William T GunningCenter for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).ORCID 0000-0002-4190-2479
Matam Vijay-KumarCenter for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).ORCID 0000-0002-8732-0167
Venkatesha BasrurDepartment of Pathology, Proteomics Resource Facility, University of Michigan, Ann Arbor (V.B.).ORCID 0000-0002-0853-9655
Ivana de la SernaDepartment of Cell and Cancer Biology, University of Toledo College of Medicine and Life Sciences, OH (I.d.l.S.).ORCID 0000-0002-6429-287X
Bina JoeCenter for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (J.M., S.A., I.M., S.C., X.M., B.S.Y., B.M., R.T., T.Y., P.S., W.T.G., M.V.-K., B.J.).ORCID 0000-0002-2385-7061

Funding

Genetic, Epigenetic and Dietary Salt effects on Microbiota and HypertensionR01HL143082 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI JOE, BINA · 2018 to 2021
$2.6M
Conjugated bile acids as nutritionally re-programmable antihypertensive metabolitesR01HL171401 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI BINA JOE · 2024 to 2026
$2.3M
Role of neutrophil extracellular traps (NETs) in Inflammatory bowel diseaseR01DK134053 · NIDDK · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI MATAM VIJAY-KUMAR · 2023 to 2026
$1.7M
NHLBI NIH HHS R01 HL143082NHLBI NIH HHS R01 HL171401NIDDK NIH HHS R01 DK134053
6 · The paper itself

Abstract

backgroundPreviously, we demonstrated that the ketone body, β-hydroxybutyrate, is a potent antihypertensive and reno-protective metabolite in Dahl Salt-Sensitive rats. However, the mechanism by which β-hydroxybutyrate confers these beneficial effects is understudied. Here we focused on determining whether the reno-protective effect of β-hydroxybutyrate is due to its known ability to epigenetically remodel chromatin via histone β-hydroxybutyrylation.

methodsWe used the same animal protocol previously used for the discovery of the reno-protective effect of β-hydroxybutyrate. Briefly, postweaning, male and female Dahl Salt-Sensitive rats were split into 2 groups and supplemented with or without 1,3-butanediol for 6 weeks. At euthanasia, circulating β-hydroxybutyrate was quantitated. Renal homogenates were examined for histone 3 lysine 9 β-hydroxybutyrylation, chromatin occupancy, transcriptomic and proteomic profiles with validations.

resultsRats supplemented with 1,3-butanediol had higher circulating β-hydroxybutyrate, renal histone β-hydroxybutyrylation, and significant remodeling of chromatin. Notably, regions of the genome associated with lipid catabolism were predominantly in an open chromatin configuration, leading to active transcription and translation. The most highly upregulated gene actively transcribed and translated was

conclusionsThese results reveal that renal epigenetic histone β-hydroxybutyrylation is a novel mechanism by which transcriptional regulation of both energy metabolism and immune function occur concomitantly and contribute to renoprotection in the hypertensive Dahl rat.

Indexed as

3-Hydroxybutyric AcidEpigenesis, GeneticHistonesHypertensionKidneyAnimalsButylene GlycolsDisease Models, AnimalFemaleMaleRatsRats, Inbred Dahl1,3-butylene glycol3-Hydroxybutyric AcidButylene GlycolsHistoneschromatin remodelingenergy metabolismhistoneshypertensionketoneskidney

Identifiers

PMID40726393
PMCPMC12444880

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.