scholarly journals Redirection of Epithelial Immune Responses by Short-Chain Fatty Acids through Inhibition of Histone Deacetylases

2015 ◽  
Vol 6 ◽  
Author(s):  
May Young Lin ◽  
Marcel R. de Zoete ◽  
Jos P. M. van Putten ◽  
Karin Strijbis
Keyword(s):  
Fatty Acids ◽  
Immune Responses ◽  
Histone Deacetylases ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

In Silicoandin VitroInteractions between Short Chain Fatty Acids and Human Histone Deacetylases

Biochemistry ◽  
2017 ◽  
Vol 56 (36) ◽  
pp. 4871-4878 ◽  
Author(s):  
Rou Hui Ho ◽  
James Chun Yip Chan ◽  
Hao Fan ◽  
Dorinda Yan Qin Kioh ◽  
Bee Wah Lee ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Histone Deacetylases ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

scholarly journals Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism

2020 ◽  
Vol 21 (17) ◽  
pp. 6356 ◽  
Author(s):  
Jin He ◽  
Peiwen Zhang ◽  
Linyuan Shen ◽  
Lili Niu ◽  
Ya Tan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Histone Deacetylases ◽  
Anaerobic Fermentation ◽  
Short Chain Fatty Acids ◽  
Biological Properties ◽  
Short Chain ◽  
Signalling Pathways ◽  
Glucose And Lipid Metabolism ◽  
Chain Fatty Acids

Short-chain fatty acids (SCFAs), particularly acetate, propionate and butyrate, are mainly produced by anaerobic fermentation of gut microbes. SCFAs play an important role in regulating energy metabolism and energy supply, as well as maintaining the homeostasis of the intestinal environment. In recent years, many studies have shown that SCFAs demonstrate physiologically beneficial effects, and the signalling pathways related to SCFA production, absorption, metabolism, and intestinal effects have been discovered. Two major signalling pathways concerning SCFAs, G-protein-coupled receptors (GPRCs) and histone deacetylases (HDACs), are well recognized. In this review, we summarize the recent advances concerning the biological properties of SCFAs and the signalling pathways in inflammation and glucose and lipid metabolism.

scholarly journals Short-chain fatty acids activate acetyltransferase p300

2021 ◽  
Author(s):  
Sydney Thomas ◽  
John Denu
Keyword(s):  
Fatty Acids ◽  
Histone Deacetylases ◽  
Quantitative Proteomics ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Physiological Processes ◽  
Low Levels ◽  
Underlying Mechanisms ◽  
Chain Fatty Acids ◽  
Acetyltransferase P300

Short-chain fatty acids (SCFAs) acetate, propionate, and butyrate are produced in large quantities by the gut microbiome and contribute to a wide array of physiological processes. While the underlying mechanisms are largely unknown, many effects of SCFAs have been traced to changes in the cell’s epigenetic state. Here, we systematically investigate how SCFAs alter the epigenome. Using quantitative proteomics of histone modification states, we identified rapid and sustained increases in histone acetylation after addition of butyrate or propionate, but not acetate. While decades of prior observations would have suggested that hyperacetylation induced by SCFAs are attributed to inhibition of histone deacetylases (HDACs), we found that propionate and butyrate instead activate the acetyltransferase p300. Propionate and butyrate are rapidly converted to the corresponding acyl-CoAs which are then used by p300 to catalyze auto-acylation of the autoinhibitory loop, activating the enzyme for histone/protein acetylation. This data challenges the long-held belief that SCFAs mainly regulate chromatin by inhibiting HDACs, and instead reveals a previously unappreciated mechanism of HAT activation that can explain how even low levels of SCFAs alter global chromatin states.

Biological functions of SLC5A8, a candidate tumour suppressor

2005 ◽  
Vol 33 (1) ◽  
pp. 237-240 ◽  
Author(s):  
V. Ganapathy ◽  
E. Gopal ◽  
S. Miyauchi ◽  
P.D. Prasad
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Histone Deacetylases ◽  
Short Chain Fatty Acids ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Short Chain ◽  
Bacterial Fermentation ◽  
Candidate Tumour Suppressor ◽  
Chain Fatty Acids

SLC5A8 is a candidate tumour suppressor gene that is silenced in colon cancer, gastric cancer and possibly other cancers in humans. This gene codes for a transporter belonging to the Na+/glucose co-transporter gene family (SLC5). The cancer-associated silencing of the gene involves hypermethylation of CpG islands present in exon 1 of the gene. SLC5A8 is expressed in colon, ileum, kidney and thyroid gland. The protein coded by the gene mediates the Na+-coupled and electrogenic transport of a variety of monocarboxylates, including short-chain fatty acids, lactate and nicotinate. It may also transport iodide. The normal physiological function of this transporter in the intestinal tract and kidney is likely to facilitate the active absorption of short-chain fatty acids, lactate and nicotinate. One of the short-chain fatty acids that serves as a substrate for SLC5A8 is butyrate. This fatty acid is an inhibitor of histone deacetylases and is known to induce apoptosis in a variety of tumours including colonic tumour. Since butyrate is produced in the colonic lumen at high concentrations by bacterial fermentation of dietary fibre, we speculate that the ability of SLC5A8 to mediate the entry of this short-chain fatty acid into colonic epithelial cells underlies the potential tumour suppressor function of this transporter.

scholarly journals Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Rachel Fellows ◽  
Jérémy Denizot ◽  
Claudia Stellato ◽  
Alessandro Cuomo ◽  
Payal Jain ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Histone Deacetylases ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

scholarly journals Differing roles for short chain fatty acids and GPR43 agonism in the regulation of intestinal barrier function and immune responses

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0180190 ◽  
Author(s):  
Warren N. D’Souza ◽  
Jason Douangpanya ◽  
Sharon Mu ◽  
Peter Jaeckel ◽  
Ming Zhang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Immune Responses ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Intestinal Barrier Function ◽  
Chain Fatty Acids

scholarly journals Short-chain fatty acids activate acetyltransferase p300

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sydney P Thomas ◽  
John M Denu
Keyword(s):  
Fatty Acids ◽  
Histone Deacetylases ◽  
Quantitative Proteomics ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Physiological Processes ◽  
Low Levels ◽  
Underlying Mechanisms ◽  
Chain Fatty Acids ◽  
Acetyltransferase P300

Short-chain fatty acids (SCFAs) acetate, propionate, and butyrate are produced in large quantities by the gut microbiome and contribute to a wide array of physiological processes. While the underlying mechanisms are largely unknown, many effects of SCFAs have been traced to changes in the cell’s epigenetic state. Here, we systematically investigate how SCFAs alter the epigenome. Using quantitative proteomics of histone modification states, we identified rapid and sustained increases in histone acetylation after addition of butyrate or propionate, but not acetate. While decades of prior observations would have suggested that hyperacetylation induced by SCFAs are attributed to inhibition of histone deacetylases (HDACs), we found that propionate and butyrate instead activate the acetyltransferase p300. Propionate and butyrate are rapidly converted to the corresponding acyl-CoAs which are then used by p300 to catalyze auto-acylation of the autoinhibitory loop, activating the enzyme for histone/protein acetylation. This data challenges the long-held belief that SCFAs mainly regulate chromatin by inhibiting HDACs, and instead reveals a previously unknown mechanism of HAT activation that can explain how an influx of low levels of SCFAs alters global chromatin states.

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