Protective effect of peroxisome proliferator-activated receptor- in regulating the early inflammation response to extended hepatectomy from a comparative transcriptomic analysis

The regulation mechanism of small-for-size syndrome remains unclear. Thus, we aimed to analyze the molecular profiles following extended hepatectomy and identify the therapeutic target. Major hepatectomy and extended hepatectomy were performed in the rat model, and the remnant livers were obtained dynamically for the high-throughput transcriptome analysis to identify the differentially expressed genes (DEGs). The general framework for weighted gene co-expression network analysis (WGCNA) was employed to explore the expression patterns of DEGs. As result, WGCNA identified 10 distinct gene co-expression modules according to the correlation between module eigengene and different postoperative time-points. The magenta module and the lightcyan module were found positively correlated with not extended hepatectomy but major hepatectomy. In the lightcyan module, peroxisome proliferator-activated receptor- (PPAR) was selected and verified the down-regulation in the remnant liver following extended hepatectomy in rats and humans. Besides, administration of PPAR agonist attenuated hepatic inflammation injury while PPAR antagonist increased liver inflammation injury after extended hepatectomy in rats, marked by the significantly changed aminotransferases, tumor necrosis factor- and interleukin-6 levels in the plasm, and histological Suzuki criteria. Consequently, DEGs and their molecular profiles after extended hepatectomy were identified, and PPAR might be a potential therapy target for small-for-size syndrome.