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

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.

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