Letter to the editor: Hepatocyte proliferation peak and β‐oxidation in liver regeneration after partial hepatectomy

To the editor, We read with great interest the article by Hall et al.[1] They stated that to mimic the peak of hepatocyte proliferation during liver regeneration, mice were sacrificed 3 days after two‐thirds partial hepatectomy.[1] However, the peak of hepatocyte proliferation occurs between 1.5 and 2 days in mice based on previous studies.[2] And different cell types also have various peaks of proliferation during liver regeneration after hepatectomy.[2] The statement could lead to relatively one‐sided conclusions. Furthermore, Hall et al. claimed that β‐oxidation was reduced overall in proliferating hepatocytes.[1] However, it is reported that the respiratory exchange ratio markedly dropped and that lipid β‐oxidation was the favored energy source for regenerating liver within the first 32 h in mice after two‐thirds partial hepatectomy and then recovered toward prehepatectomy levels from 32 h onward.[3] The process of liver regeneration after two‐thirds partial resection is divided into three phases—initiation, progression, and termination—whose metabolic function is varied across different phases.[2–4] This article by Hall et al. revealed the β‐oxidation status of proliferating hepatocytes in only one phase of liver regeneration in mice, which did not fully present the lipid metabolic status across phases of liver regeneration. In addition, the physiological process of transient regeneration–associated steatosis of hepatocytes inevitably develops within 48 h after two‐thirds hepatectomy in mice,[3,5] and we believe that the lipid components of hepatocytes could be varied across different phases of liver regeneration, which may have a great impact on the reliability of the critical conclusions of the article by Hall et al. Therefore, an unrepresentative time point of hepatocyte proliferation was selected in the article by Hall et al., and multiple regeneration time points should be explored in this study to obtain solid conclusions. The dynamic metabolic process of proliferating hepatocytes should be given more attention in a partial hepatectomy model. CONFLICT OF INTEREST Nothing to report. AUTHOR CONTRIBUTIONS Fuchen Liu and Wenli Zhang shared co‐first authorship. Conceptualization: Hui Liu. Drafting and writing: Fuchen Liu, Wenli Zhang, and Hui Liu.