Sodium Butyrate Supplementation Alleviates the Adaptive Response to Inflammation and Modulates Fatty Acid Metabolism in Lipopolysaccharide-Stimulated Bovine Hepatocytes

Tianle Xu, Nana Ma, Yan Wang, Xiaoli Shi, Guangjun Chang, Juan J. Loor, Xiangzhen Shen

Research output: Contribution to journalArticle

Abstract

This study aimed to evaluate whether sodium butyrate (SB) attenuates the hepatic response to LPS-induced inflammation in bovine hepatocytes. Hepatocytes isolated from cows at ∼160 days in milk (DIM) were exposed to 0.5 mmol/L SB for 18 h as pretreatment. Cells pretreated with SB were used for the SB group, and those subjected to 4 μg/mL lipopolysaccharide (LPS) challenge for 6 h were used for the lipopolysaccharide pretreated with SB (LSB) group. The LPS-challenged hepatocytes showed increases in TNF-α and IL-6 production in culture medium (37 ± 11, P < 0.05); these increases were attenuated by pretreatment with SB in the LSB group (267 ± 4, P < 0.05). Compared to that in LPS-treated cells, the phospho-p65 and phospho-IκBα protein expression and nuclear translocation were suppressed when SB was added. Genes (SREBP1c, SCD1, and DGAT1) and proteins (SREBP1c and SCD1) related to fatty acid metabolism were upregulated in LSB cells compared to those in LPS-treated cells (P < 0.05). The ratios of phospho-AMPKα to AMPKα (0.32 ± 0.03 vs 0.70 ± 0.07) and phospho-ACCα to ACCα were decreased (0.81 ± 0.06 vs 2.06 ± 0.16) (P < 0.05) in the LSB group. SB pretreatment reversed the histone H3 deacetylation that was increased by LPS stimulation in bovine hepatocytes (0.54 ± 0.02 vs 1.27 ± 0.11, P < 0.05). Our results suggest that SB pretreatment suppresses the hepatocyte changes that occur during the LPS-induced inflammatory response, which is accompanied by enhanced fatty acid synthesis, downregulated fatty acid oxidation, and histone H3 deacetylation, thus neutralizing the negative effects of infection.

Original languageEnglish (US)
Pages (from-to)6281-6290
Number of pages10
JournalJournal of Agricultural and Food Chemistry
Volume66
Issue number25
DOIs
StatePublished - Jun 27 2018

Keywords

  • bovine hepatocytes
  • fatty acid metabolism
  • histone deacetylation
  • inflammation
  • sodium butyrate

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

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