In addition to the other risk factors associated with metabolic syndrome, dysregulation of lipid metabolism in the liver causes nonalcoholic fatty liver disease. The subsequent progression to nonalcoholic steatohepatitis (NASH) is a significant problem whose etiology is poorly understood. In this issue, Kong et al., provide evidence that farnesoid X receptor (FXR) deficiency can contribute to NASH. A common model for hyperlipidemia is the LDR-/- mice; these were crossed with FXR-/- mice, and both strains were fed standard and high-fat chow. Although hyperlipidemia was observed both strains, livers of mice fed a high-fat diet exhibited hepatocyte ballooning; however, only the LDR-/-FXR-/- showed inflammatory cell foci in liver. The livers of the double knockout mice also exhibited increased inflammatory and fibrosis markers when fed a high-fat diet. These results demonstrate a role for the FXR in NASH and suggest that activation of the FXR could have therapeutic utility in the prevention of NASH.
See article at J Pharmacol Exp Ther 2009, 328:116–122.
- The American Society for Pharmacology and Experimental Therapeutics