Endogenous phosphatidylcholine 16:0/20:4 increases to promote liver regeneration in hepatectomy.

Liver regeneration after hepatectomy is a challenge in patients with metabolic dysfunction-associated steatohepatitis (MASH), as well as small-for-size syndrome and ex vivo organogenesis. Endogenous lipid metabolites promoting liver regeneration are poorly understood. A 70% partial hepatectomy (PHx) was performed in mice with healthy and MASH liver. Biomarkers promoting liver regeneration were explored using hepatic lipidomics followed by structural identification. The functional validation was performed in in vivo and in vitro models. Liver regeneration post-PHx peaked earlier in the MASH liver than that in the healthy liver. Phosphatidylcholine (PC) (16:0/20:4) increased in both MASH liver and non-MASH liver, and it promoted the proliferation of Hepa 1-6, Huh-7, human liver organoids, and mouse PHx models. In patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and those undergoing hepatectomy, the serum PC (16:0/20:4) also increased, supporting the findings in this work. PC (16:0/20:4) is an endogenous lipid biomarker promoting liver regeneration which increased during hepatectomy in healthy and MASH liver.