The study shows that the small protein humanin can protect liver cells from fat buildup and insulin problems caused by a fatty acid, working through a pathway that turns on AMPK and turns off mTOR. This was done in cell cultures, not in people, so it’s an early‑stage finding.

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains unclear. Humanin (HN), a cytoprotective polypeptide, reportedly exhibits neuroprotective effects via suppression of inflammation and improvement of insulin resistance in neurons. This study aim was to investigate effects of HN on lipid accumulation in the hepatocytes and insulin signaling, and explore the underlying mechanisms. Protein expression levels were analyzed by Western blotting. Hepatic lipid accumulation was confirmed by Oil red-O staining. We found that HN-treatment ameliorated palmitate-induced lipid accumulation, expression of lipogenesis-associated genes (processed SREBP1, FAS, and SCD1), cell death, and caspase 3 activity in hepatocytes in a dose-dependent manner. Additionally, HN attenuated palmitate-induced impairment of insulin signaling. HN enhanced AMPK phosphorylation, whereas it suppressed palmitate-induced phosphorylation of mTOR. AMPK knockdown by siRNA neutralized the effects of HN on palmitic acid-treated hepatocytes. Collectively, HN prevents palmitate-induced hepatic lipid accumulation, apoptosis, and insulin resistance via AMPK-mediated suppression of the mTOR/SREBP1 pathway, suggesting that it may serve as a potential therapeutic agent in NAFLD treatment.