title: Unravelling the pathogenesis of fatty liver disease: patatin-like  phospholipase domain-containing 3 protein.
abstract: OBJECTIVE
  Hepatic steatosis is a leading cause of adult and paediatric liver disease and is inextricably linked to obesity, insulin resistance and cardiovascular disease. Here we summarize our current understanding of the role of the patatin-like phospholipase domain-containing 3 gene (PNPLA3) in hepatic steatosis.
  
  
  RESULTS
  Multiple studies have revealed an association between the common I148M variant in PNPLA3 and increased hepatic fat. In the presence of obesity and chronic alcohol intake, the variant is associated with even more striking phenotypes such as hepatitis and cirrhosis, respectively. These findings suggest that genetic variants in PNPLA3 predispose towards hepatic steatosis and, in the context of other environmental stressors, its progression to irreversible liver failure. PNPLA3 is predominantly expressed in human liver and adipose tissue, possesses both lipolytic and lipogenic activity in vitro and localizes to the surface of lipid droplets in heptocytes. The 148M mutant protein has reduced lipolytic activity, with attendant increased cellular triglyceride accumulation. However, the precise physiological role of PNPLA3 remains mysterious.
  
  
  CONCLUSIONS
  Recent studies have implicated PNPLA3 in the pathogenesis of hepatic steatosis. Attempts to describe its function in vivo may provide us with both an opportunity to understand and a strategy to overcome this leading cause of human morbidity.
authors.affiliation: Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. sr517@medschl.cam.ac.uk
authors.forename: Stefano
authors.initials: S
authors.lastname: Romeo
authors.forename: Isabel
authors.initials: I
authors.lastname: Huang-Doran
authors.forename: Marco Giorgio
authors.initials: MG
authors.lastname: Baroni
authors.forename: Anna
authors.initials: A
authors.lastname: Kotronen
mesh_terms: D000818:Animals; D005234:Fatty Liver / Q000201:enzymology* / Q000209:etiology* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009154:Mutation; D054512:Phospholipases A2, Calcium-Independent / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D054512:Phospholipases A2, Calcium-Independent