Disruption of hepatic small heterodimer partner induces dissociation of steatosis and inflammation in experimental nonalcoholic steatohepatitis.

ABSTRACT: Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide and is characterized by steatosis, inflammation, and fibrosis. The molecular mechanisms underlying NASH development remain obscure. The nuclear receptor small heterodimer partner (Shp) plays a complex role in lipid metabolism and inflammation. Here, we sought to determine SHP's role in regulating steatosis and inflammation in NASH. Shp deletion in murine hepatocytes (Shp^Hep-/-) resulted in massive infiltration of macrophages and CD4⁺ T cells in the liver. Shp^Hep-/- mice developed reduced steatosis, but surprisingly increased hepatic inflammation and fibrosis after being fed a high-fat, -cholesterol, and -fructose (HFCF) diet. R

SUBMITTER: Magee N 

PROVIDER: S-EPMC6983844 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature