title: Pathophysiology of Nonalcoholic Fatty Liver Disease: Lifestyle-Gut-Gene Interaction.
abstract: BACKGROUND
  The accumulation of fat droplets in the hepatic parenchyma is driven by several factors, synergistically acting to increase triglyceride flow to the liver (diet and metabolic factors, endotoxemia from gut microbiota, genetic factors).
  
  
  CONCLUSIONS
  In the presence of unhealthy lifestyles and behavioral factors, leading to enlarged adipose tissue and insulin resistance (IR), both lipolysis and de novo lipogenesis are expected to increase the risk of hepatic lipid depots, in association with high calorie (either high-fat or high-carbohydrate) diets. The gut microbiota may also be involved via obesity, IR and hepatic inflammation generated by gut-derived toxic factors. Finally, several data also support a primary role of genetic factors. A few gene polymorphisms have also been associated with the risk of nonalcoholic fatty liver disease development and nonalcoholic steatohepatitis progression to more fibrosis and advanced liver disease. In a few cases (e.g., patatin-like phospholipase domain-containing 3/adiponutrin), steatosis carries a high risk of both liver disease and cardiovascular morbidity/mortality; in other cases (e.g., transmembrane 6 superfamily 2 human gene), dissociation has been observed between the increased risk of liver disease versus cardiovascular disease.
  
  
  CONCLUSIONS
  A variable interplay between the genetic background and the metabolic milieu is the likely physiopathologic mechanism involved in individual cases, which must be considered for implementing effective treatment strategies.
authors.affiliation: Unit of Metabolic Diseases and Clinical Dietetics, 'Alma Mater' University, Bologna, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Mazzotti
authors.forename: Maria Turchese
authors.initials: MT
authors.lastname: Caletti
authors.forename: Anna Simona
authors.initials: AS
authors.lastname: Sasdelli
authors.forename: Lucia
authors.initials: L
authors.lastname: Brodosi
authors.forename: Giulio
authors.initials: G
authors.lastname: Marchesini
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D002318:Cardiovascular Diseases / Q000209:etiology; D004032:Diet / Q000009:adverse effects; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007333:Insulin Resistance; D008019:Life Style; D050155:Lipogenesis; D008066:Lipolysis; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D009765:Obesity / Q000150:complications / Q000378:metabolism; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014280:Triglycerides