Sodium Butyrate Ameliorates High-Fat-Diet-Induced Non-alcoholic Fatty Liver Disease through Peroxisome Proliferator-Activated Receptor α-Mediated Activation of β Oxidation and Suppression of Inflammation

Peroxisome proliferator-activated receptor a (PPAR alpha) plays a protective role against non-alcoholic fatty liver disease (NAFLD). Sodium butyrate (NaB) has been shown to alleviate NAFLD, yet whether and how PPAR alpha is involved in the action of NaB remains elusive. In this study, NaB administration alleviated high-fat-diet-induced NAFLD in adult rats, with a decrease of hepatic triglyceride content from 108.18 +/- 5.77 to 81.34 +/- 7.94 mu g/mg (p < 0.05), which was associated with a significant activation of PPAR alpha. Nuclear factor k-light-chain-enhancer of activated B cell (NF-kB)-mediated nucleotide-binding domain-like receptor protein 3 signaling and pro-inflammatory cytokine release were diminished by NaB treatment. NaB-induced PPAR alpha upregulation coincided with a reduced protein content of histone deacetylase 1 and promoted histone H3 acetyl K9 (H3K9Ac) modification on the promoter of PPAR alpha, whereas NaB-induced suppression of inflammation was linked to significantly increased PPAR alpha binding with p-p65. NaB acts as a histone deacetylase inhibitor to upregulate PPAR alpha expression with enhanced H3K9Ac modification on it promoter. NaB-induced PPAR alpha activation stimulates fatty acid beta oxidation and inhibits NF-kB-mediated inflammation pathways via protein-protein interaction, thus contributing to amelioration of high-fatdiet-induced NAFLD in adult rats.