Sodium butyrate attenuates lipid metabolism disorder via improving mitochondrial function and activating autophagy in...

Hepatic steatosis is the main characteristic in fatty liver hemorrhagic syndrome (FLHS), sodium butyrate (NaB) has been shown to modulate hepatic metabolism, alleviate oxidative stress and restore mitochondrial function. However, the effects of NaB on avian cellular models have yet to be thoroughly investigated. Leghorn male hepatocyte (LMH) cells, due to their immortal characteristics, provide a stable and reliable model for studying avian hepatocyte steatosis. Steatosis was induced by treating LMH cells with 400 μM oleic acid (OA), while 1 mM NaB was applied to evaluate its potential protective effects against OA-induced lipid accumulation. Cells were divided into four groups: the Control group, OA group, OA+NaB group, and NaB group. The results revealed that NaB reduced lipid accumulation, as evidenced by decreased cholesterol and triglyceride levels; Additionally, NaB upregulated the expression of genes associated with fatty acid catabolism, while downregulating those related to fatty acid synthesis. NaB alleviated OA-induced oxidative stress by increasing superoxide dismutase activity and reducing malondialdehyde and reactive oxygen species levels. NaB preserved mitochondrial integrity and maintained mitochondrial membrane potential, preventing OA-induced impairment. NaB attenuated apoptosis induced by OA treatment, as evidenced by a decrease in the Bax expression, the Bax/Bcl-2 expression ratio and a lower percentage of apoptotic cells. NaB also promoted autophagosome formation and modulated the LKB1-AMPK-mTOR signaling pathway, increasing the LC3Ⅱ/LC3Ⅰ protein ratio while reducing P62 protein expression. Consequently, NaB protected LMH cells from OA-induced lipid metabolism disorders by improving mitochondrial function and activating autophagy, suggesting its potential as a promising feed additive for preventing lipid metabolism disorders in poultry production.