Statistics from Altmetric.com
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. It comprises a spectrum ranging from bland steatosis or NAFL to non-alcoholic steatohepatitis (NASH) with or without fibrosis. There is a general consensus that patients with NAFLD have a very slow disease progression (if any). By contrast, patients with NASH can exhibit histological progression and can develop fibrosis, cirrhosis and hepatocellular carcinoma. Parenchymal inflammation is an important determinant of the severity and progression of the disease.
Increased fatty acid flux to the liver, from dietary absorption and from the adipose tissue, owing to insulin resistance, is a main contributor to increased hepatic lipid content. In addition, increased de novo lipogenesis, impaired mitochondrial fatty acid oxidation or decreased export of very low density lipoprotein triglyceride all play a part. Ligand-activated nuclear receptors control several key steps in lipid metabolism as well as inflammation and fibrogenesis and thus are potentially crucial players in NAFLD/NASH pathogenesis.1 One of those nuclear receptors is the bile salt sensor farnesoid X receptor (FXR). Besides regulating cholesterol and bile salt homeostasis, FXR is a key regulator of hepatic lipid metabolism. FXR, via induction of a short heterodimer partner, represses de novo lipogenesis. It induces peroxisome proliferator activated receptor (PPAR)α, and thus stimulates fatty acid β oxidation. The role of FXR is emphasised by the development of hepatosteatosis and hyperlipidaemia in FXR−/− mice.2 ,3 …
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.