Prominent action of butyrate over beta-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule

Autor: Martyna Wojtala, Aneta Balcerczyk, Team1 Carmen, Hubert VIDAL, Team2 Carmen, Luciano Pirola, Carmen Lab
Přispěvatelé: Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, University of Lódź, INSERM institutional funding, Polish Ministry of Science and Higher Education, project grant Iuventus Plus [IP2012 0390 72], L'Oreal for Women in Science, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), CarMeN, laboratoire, Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Pirola, Luciano
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Transcription
Genetic
sirt1
[SDV]Life Sciences [q-bio]
Anti-Inflammatory Agents
lcsh:Medicine
Hydroxybutyrates
B signaling pathway
muscle-cells
Mice
angiogenesis
0302 clinical medicine
Transcriptional regulation
lcsh:Science
Multidisciplinary
biology
Chemistry
Forkhead Box Protein O3
Histone deacetylase inhibitor
Acetylation
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Cell biology
[SDV] Life Sciences [q-bio]
Butyrates
nlrp3 inflammasome
Histone
2-hydroxyisobutyrylation
medicine.drug_class
SOD2
expression
metabolism
Butyrate
Article
Histone Deacetylases
03 medical and health sciences
medicine
Animals
Humans
Inflammation
lcsh:R
Endothelial Cells
Rats
Histone Deacetylase Inhibitors
Oxidative Stress
030104 developmental biology
Gene Expression Regulation
biology.protein
lcsh:Q
Metallothionein
Cytokine secretion
Histone deacetylase
030217 neurology & neurosurgery
Zdroj: Scientific Reports
Scientific Reports, Nature Publishing Group, 2019, 9 (1), pp.742. ⟨10.1038/s41598-018-36941-9⟩
Sci Rep
Sci Rep, 2019, 9 (1), pp.742. ⟨10.1038/s41598-018-36941-9⟩
Scientific Reports (9), . (2019)
Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
ISSN: 2045-2322
Popis: Butyrate and R-β-hydroxybutyrate are two related short chain fatty acids naturally found in mammals. Butyrate, produced by enteric butyric bacteria, is present at millimolar concentrations in the gastrointestinal tract and at lower levels in blood; R-β-hydroxybutyrate, the main ketone body, produced by the liver during fasting can reach millimolar concentrations in the circulation. Both molecules have been shown to be histone deacetylase (HDAC) inhibitors, and their administration has been associated to an improved metabolic profile and better cellular oxidative status, with butyrate inducing PGC1α and fatty acid oxidation and R-β-hydroxybutyrate upregulating oxidative stress resistance factors FOXO3A and MT2 in mouse kidney. Because of the chemical and functional similarity between the two molecules, we compared here their impact on multiple cell types, evaluating i) histone acetylation and hydroxybutyrylation levels by immunoblotting, ii) transcriptional regulation of metabolic and inflammatory genes by quantitative PCR and iii) cytokine secretion profiles using proteome profiling array analysis. We confirm that butyrate is a strong HDAC inhibitor, a characteristic we could not identify in R-β-hydroxybutyrate in vivo nor in vitro. Butyrate had an extensive impact on gene transcription in rat myotubes, upregulating PGC1α, CPT1b, mitochondrial sirtuins (SIRT3-5), and the mitochondrial anti-oxidative genes SOD2 and catalase. In endothelial cells, butyrate suppressed gene expression and LPS-induced secretion of several pro-inflammatory genes, while R-β-hydroxybutyrate acted as a slightly pro-inflammatory molecule. Our observations indicate that butyrate induces transcriptional changes to a higher extent than R-β-hydroxybutyrate in rat myotubes and endothelial cells, in keep with its HDAC inhibitory activity. Also, in contrast with previous reports, R-β-hydroxybutyrate, while inducing histone β-hydroxybutyrylation, did not display a readily detectable HDAC inhibitor activity and exerted a slight pro-inflammatory action on endothelial cells.
Databáze: OpenAIRE
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