Effects of orally applied butyrate bolus on histone acetylation and cytochrome P450 enzyme activity in the liver of chicken – a randomized controlled trial

Nutrition & Metabolism

Korinna Huber¹  Ákos Kenéz¹  Anna Kulcsár³  György Csikó²  Zsuzsanna Neogrády³  Gábor Mátis³ 

[1] Department of Physiology, University of Veterinary Medicine, Bischofsholer Damm 15/102, D-30173, Hannover, Germany;Department of Pharmacology and Toxicology, Faculty of Veterinary Science, Szent István University, István utca 2, H-1078, Budapest, Hungary;Department of Physiology and Biochemistry, Faculty of Veterinary Science, Szent István University, István utca 2, H-1078, Budapest, Hungary

关键词: Cytochrome P450 enzymes;    Epigenetics;    Histone hyperacetylation;    Histone deacetylase inhibitor;    Butyrate;    Short chain fatty acids;   

Others  :  811261
DOI  :  10.1186/1743-7075-10-12

 received in 2012-10-03, accepted in 2013-01-11,  发布年份 2013

【 摘 要 】

Background

Butyrate is known as histone deacetylase inhibitor, inducing histone hyperacetylation in vitro and playing a predominant role in the epigenetic regulation of gene expression and cell function. We hypothesized that butyrate, endogenously produced by intestinal microbial fermentation or applied as a nutritional supplement, might cause similar in vivo modifications in the chromatin structure of the hepatocytes, influencing the expression of certain genes and therefore modifying the activity of hepatic microsomal drug-metabolizing cytochrome P450 (CYP) enzymes.

Methods

An animal study was carried out in chicken as a model to investigate the molecular mechanisms of butyrate’s epigenetic actions in the liver. Broiler chicks in the early post-hatch period were treated once daily with orally administered bolus of butyrate following overnight starvation with two different doses (0.25 or 1.25 g/kg body weight per day) for five days. After slaughtering, cell nucleus and microsomal fractions were separated by differential centrifugation from the livers. Histones were isolated from cell nuclei and acetylation of hepatic core histones was screened by western blotting. The activity of CYP2H and CYP3A37, enzymes involved in biotransformation in chicken, was detected by aminopyrine N-demethylation and aniline-hydroxylation assays from the microsomal suspensions.

Results

Orally added butyrate, applied in bolus, had a remarkable impact on nucleosome structure of hepatocytes: independently of the dose, butyrate caused hyperacetylation of histone H2A, but no changes were monitored in the acetylation state of H2B. Intensive hyperacetylation of H3 was induced by the higher administered dose, while the lower dose tended to increase acetylation ratio of H4. In spite of the observed modification in histone acetylation, no significant changes were observed in the hepatic microsomal CYP2H and CYP3A37 activity.

Conclusion

Orally added butyrate in bolus could cause in vivo hyperacetylation of the hepatic core histones, providing modifications in the epigenetic regulation of cell function. However, these changes did not result in alteration of drug-metabolizing hepatic CYP2H and CYP3A37 enzymes, so there might be no relevant pharmacoepigenetic influences of oral application of butyrate under physiological conditions.

【 授权许可】

   
2013 Matis et al.; licensee BioMed Central Ltd.

【 图 表 】

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