Evidence map›Paper›PMID 36555149›Full record

ArticleInternational journal of molecular sciences2022

Butyrate Lowers Cellular Cholesterol through HDAC Inhibition and Impaired SREBP-2 Signalling.

Stephanie Bridgeman, Hon Chiu Woo, Philip Newsholme, Cyril Mamotte

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
5.2field-weighted citation impact, top 4% of its field
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

20 citing papers in PubMed, 27 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Stephanie BridgemanCurtin Health Innovation Research Institute and Curtin Medical School, Curtin University, Bentley, WA 6102, Australia.
Hon Chiu WooCurtin Health Innovation Research Institute and Curtin Medical School, Curtin University, Bentley, WA 6102, Australia.
Philip NewsholmeCurtin Health Innovation Research Institute and Curtin Medical School, Curtin University, Bentley, WA 6102, Australia.ORCID 0000-0002-0500-6984
Cyril MamotteCurtin Health Innovation Research Institute and Curtin Medical School, Curtin University, Bentley, WA 6102, Australia.
Curtin University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In animal studies, HDAC inhibitors such as butyrate have been reported to reduce plasma cholesterol, while conferring protection from diabetes, but studies on the underlying mechanisms are lacking. This study compares the influence of butyrate and other HDAC inhibitors to that of statins on cholesterol metabolism in multiple cell lines, but primarily in HepG2 hepatic cells due to the importance of the liver in cholesterol metabolism. Sodium butyrate reduced HepG2 cholesterol content, as did sodium valproate and the potent HDAC inhibitor trichostatin A, suggesting HDAC inhibition as the exacting mechanism. In contrast to statins, which increase SREBP-2 regulated processes, HDAC inhibition downregulated SREBP-2 targets such as HMGCR and the LDL receptor. Moreover, in contrast to statin treatment, butyrate did not increase cholesterol uptake by HepG2 cells, consistent with its failure to increase LDL receptor expression. Sodium butyrate also reduced ABCA1 and SRB1 protein expression in HepG2 cells, but these effects were not consistent across all cell types. Overall, the underlying mechanism of cell cholesterol lowering by sodium butyrate and HDAC inhibition is consistent with impaired SREBP-2 signalling, and calls into question the possible use of butyrate for lowering of serum LDL cholesterol in humans.

Indexed as

Hydroxymethylglutaryl-CoA Reductase InhibitorsButyric AcidCholesterolHep G2 CellsHistone Deacetylase InhibitorsHumansReceptors, LDLSterol Regulatory Element Binding Protein 1Sterol Regulatory Element Binding Protein 2Butyric AcidCholesterolHistone Deacetylase InhibitorsHydroxymethylglutaryl-CoA Reductase InhibitorsReceptors, LDLSterol Regulatory Element Binding Protein 1Sterol Regulatory Element Binding Protein 2butyratecholesterolHDAC inhibitorsLDLSREBP-2statins

Identifiers

PMID36555149
PMCPMC9779842
OpenAlexW4311849707

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.