Development of NASH in Obese Mice is Confounded by Adipose Tissue Increase in Inflammatory NOV and Oxidative Stress

Figure 8

Schematic description of the HO-1 mediated induction of adipose tissue of HF fed mice. As seen in right side panel, decreased HO-1 resulted in an increase of hepatic heme, hepcidin, which is associated with the development and progression of obesity-induced NASH, fibrosis via mitochondrial dysfunction (fission and decreases in COX 2 and 4). Fat expansion was associated with remodeling marked by an increase in adipocyte hyperplasia and hypertrophy leading to proinflammatory molecule NOV, which is associated with a decrease of PGC-1α and insulin receptor phosphorylation and eventually development of fibrosis and NAS. In the left panel, induction of HO-1 reduced the severity of steatosis, inflammation, and fibrosis through decrease in NOV and an increase of adiponectin that resulted in the improvement of hepatic mitochondrial integrity, pAMPK-pAKT, and insulin receptor phosphorylation that all in concert leads to an improvement in hepatic function and steatosis.