The Role of PPARs in Inflammation

Inflammation is the key driving force for the progression of NAFLD (non-alcoholic fatty liver disease). It drives the progression from simple steatosis, which means fattening of the liver to an inflamed state of steatohepatitis, and this is associated with the progression, for instance of liver fibrosis and ultimately later cirrhosis and hepatocellular carcinoma. So targeting inflammation is the key aspect of any treatment against NASH (non-alcoholic steatohepatitis). PPARs  are nuclear receptors that actually bind fatty acids and so they are very much involved in the metabolism of the cells, but they also have a role in inflammation because PPARs (Peroxisome proliferator-activated receptors) often block inflammatory pathways. That has been shown for many cells, for instance for parasites that are very stressed and PPARs help to calm down the parasite and block inflammatory responses. Also for other key inflammatory cells like macrophages as well as there being certain isoforms of the PPAR and they can be targeted by specific agonists. We know that these agonists of PPAR pathways will block inflammatory responses and ultimately that should help to revert as steatohepatitis to a more simple and less progressive form of the disease such as steatosis.