The Metabolic Reprogramming Profiles in the Liver Fibrosis of Mice Infected with Schistosoma japonicum.

Disordered glucose and lipid metabolism contributes to the progression of several liver diseases, while the upregulation of phosphatase and tensin homology deleted on chromosome ten (PTEN), a well-known tumour suppressor gene, can improve the condition through metabolic programming. This study first characterized the metabolic profiles and the involvement of PTEN in the hepatic fibrosis induced by Schistosoma japonicum (S. japonicum) to provide a novel clue for metabolism-targeted treatment. Compared with control mice, infected mice showed infiltrated immune cells in their livers, increased levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased glucose levels in their sera. The expression of key enzymes in the glycolytic pathway was significantly increased, and the expression of gluconeogenic genes was distinctly decreased. Moreover, the infection upregulated the hepatic expression of enzymes involved in fatty acid oxidation, which was consistent with the decreased number of lipid droplets in livers and the lowered levels of triglyceride in sera. Consistently, PTEN and its downstream signalling were significantly inhibited. In vitro, soluble egg antigen (SEA) downregulated the expression of PTEN in both the macrophage RAW264.7 cell line and the murine hepatocellular carcinoma HEP1-6 cell line, and induced a metabolic phenotype similar to the in vivo results. Overall, this study showed that S. japonicum infection induced the reprogramming of glucose and lipid metabolism in mice during the period of liver fibrosis and that SEA could act as a modulator to trigger such a metabolic switch in macrophages and hepatocytes. PTEN might play an essential role in mediating these metabolic reprogramming events.

Citation

Xin-Yu Qian, Wei-Min Ding, Qing-Qing Chen, Xin Zhang, Wen-Qing Jiang, Fen-Fen Sun, Xiang-Yang Li, Xiao-Ying Yang, Wei Pan. The Metabolic Reprogramming Profiles in the Liver Fibrosis of Mice Infected with Schistosoma japonicum. Inflammation. 2020 Apr;43(2):731-743

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PMID: 31907686

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