CCN1 promotes hepatic steatosis and inflammation in non-alcoholic steatohepatitis

Sci Rep. 2020 Feb 21;10(1):3201. doi: 10.1038/s41598-020-60138-8.


Non-alcoholic fatty liver disease (NAFLD) is characterized by increased uptake and accumulation of lipids in hepatocytes. Simple steatosis may progress to non-alcoholic steatohepatitis (NASH) with inflammation, hepatocellular injury and fibrosis. CCN1 is an important matrix protein that regulates cell death and promotes immune cell adhesion and may potentially control this process. The role of CCN1 in NASH remains unclear. We investigated the role of CCN1 in the pathogenesis of steatohepatitis. CCN1 upregulation was found to be closely related with steatosis in patients with NASH, obese mice and a FFA-treated hepatocyte model. Controlling the expression of CCN1 in murine NASH models demonstrated that CCN1 increased the severity of steatosis and inflammation. From the sequence results, we found that fatty acid metabolism genes were primarily involved in the MCD mice overexpressing CCN1 compared to the control. Then, the expression of fatty acid metabolism genes was determined using a custom-designed pathway-focused qPCR-based gene expression array. Expression analysis showed that CCN1 overexpression significantly upregulated the expression of fatty acid metabolism-associated genes. In vitro analysis revealed that CCN1 increased the intracellular TG content, the pro-inflammatory cytokines and the expression level of apoptosis-associated proteins in a steatosis model using murine primary hepatocytes. We identified CCN1 as an important positive regulator in NASH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Apoptosis
  • Cell Adhesion
  • Cysteine-Rich Protein 61 / genetics
  • Cysteine-Rich Protein 61 / metabolism*
  • Cytokines / metabolism
  • Fatty Liver / metabolism*
  • Fatty Liver / pathology
  • Female
  • Gastrointestinal Diseases / metabolism*
  • Gastrointestinal Diseases / pathology
  • Hepatocytes / metabolism
  • Humans
  • Inflammation / metabolism*
  • Lipid Metabolism
  • Liver / metabolism
  • Liver / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Non-alcoholic Fatty Liver Disease / pathology


  • CCN1 protein, human
  • CCN1 protein, mouse
  • Cysteine-Rich Protein 61
  • Cytokines