Dynamic Alterations of Plasma Metabolites in the Progression of Liver Regeneration after Partial Hepatectomy

Abstract

To elucidate the dynamic alterations of metabolites in rat plasma during liver regeneration and search for potential biomarkers of liver regeneration, 65 male Sprague-Dawley rats were divided into three groups: 70% partial hepatectomy group (PHx, <i>n</i> = 30), sham-operated group (Sham, <i>n</i> = 30), and pre-PHx group (pre-PHx, <i>n</i> = 5). Rats in the Sham and PHx groups were sacrificed after 30 min (min), 6 h (h), 24, 48, 72, and 168 h of surgery (<i>n</i> = 5 per time point). The gas chromatography-mass spectrometry-based metabolomic approach was used to identify the dynamic metabolites. Liver regeneration in the rats was evidenced by an increase in the liver weight/body weight ratio, expression of proliferating cell nuclear antigen, and yes-associated protein-1. Thirty-four differentially abundant metabolites between the Sham and PHx groups were identified, which were involved in arginine and proline metabolism, aminoacyl-tRNA biosynthesis, and cysteine and methionine metabolism pathways. Of these metabolites, low 1,5-anhydroglucitol may indicate proliferation of liver parenchymal cells during liver regeneration. Thus, a series of metabolic changes occurred with the progression of liver regeneration, and 1,5-anhydroglucitol could function as a novel hallmark of proliferation of liver parenchymal cells.