Exposing primary mouse hepatocytes to palmitic acid and lipopolysaccharide <i>in vitro</i>, we demonstrated that the suppression of <i>Shp</i> expression in hepatocytes is due to c-Jun N-terminal kinase (JNK) activation, which stimulates c-Jun-mediated transcriptional repression of <i>Shp</i> Interestingly, <i>in vivo</i> induction of hepatocyte-specific SHP in steatotic mouse liver ameliorated NASH progression by attenuating liver inflammation and fibrosis, but not steatosis.
These data suggest that Fxr and Shp inactivation may be beneficial to combat diet-induced obesity and uncover that hepatic SHP is necessary to promote fatty liver disease.(Hepatology 2017;66:1854-1865).
Liver E2F1 messenger RNA (mRNA) and protein expression was strongly up-regulated in human nonalcoholic steatohepatitis (NASH) and alcohol cirrhosis; the latter was inversely correlated with diminished SHP expression.