Adrenic acid suppresses liver regeneration by inhibiting Serpina1c expression

Diminished hepatocyte regeneration constitutes a fundamental pathological feature in chronic liver diseases. While elevated adrenic acid (ADA) has recently been implicated in chronic hepatopathies, its direct regulatory role in liver regeneration remained undefined. Here, we examined the effect of ADA on hepatocyte proliferation and liver regeneration. Using a murine partial hepatectomy (PHx) model, we found that systemic administration of ADA significantly impaired liver regeneration, evidenced by reduced liver-to-body weight ratios and fewer Ki67-positive hepatocytes. Mechanistically, transcriptomic analysis identified Serpina1c as a key downstream target suppressed by ADA. In vitro, ADA directly inhibited AML12 hepatocyte proliferation, an effect that was completely rescued by the overexpression of Serpina1c. Conclusively, ADA-mediated Serpina1c inhibition suppresses hepatic regeneration, while restoring its function rescues this defect, suggesting a molecularly precise therapeutic strategy.