title: Review: The role of insulin resistance in nonalcoholic fatty liver disease.
abstract: BACKGROUND
  Insulin resistance is an almost universal finding in nonalcoholic fatty liver disease (NAFLD). This review outlines the evidence linking insulin resistance and NAFLD, explores whether liver fat is a cause or consequence of insulin resistance, and reviews the current evidence for treatment of NAFLD.
  
  
  METHODS
  Evidence from epidemiological, experimental, and clinical research studies investigating NAFLD and insulin resistance was reviewed.
  
  
  RESULTS
  Insulin resistance in NAFLD is characterized by reductions in whole-body, hepatic, and adipose tissue insulin sensitivity. The mechanisms underlying the accumulation of fat in the liver may include excess dietary fat, increased delivery of free fatty acids to the liver, inadequate fatty acid oxidation, and increased de novo lipogenesis. Insulin resistance may enhance hepatic fat accumulation by increasing free fatty acid delivery and by the effect of hyperinsulinemia to stimulate anabolic processes. The impact of weight loss, metformin, and thiazolidinediones, all treatments aimed at improving insulin sensitivity, as well as other agents such as vitamin E, have been evaluated in patients with NAFLD and have shown some benefit. However, most intervention studies have been small and uncontrolled.
  
  
  CONCLUSIONS
  Insulin resistance is a major feature of NAFLD that, in some patients, can progress to steatohepatitis. Treatments aimed at reducing insulin resistance have had some success, but larger placebo-controlled studies are needed to fully establish the efficacy of these interventions and possibly others in reducing the deleterious effects of fat accumulation in the liver.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System (151), 1660 South Columbian Way, Seattle, Washington 98108, USA. kutzschn@u.washington.edu
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Utzschneider
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kahn
mesh_terms: D016207:Cytokines / Q000502:physiology; D005227:Fatty Acids / Q000032:analysis; D005234:Fatty Liver / Q000453:epidemiology / Q000209:etiology* / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000209:etiology; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000737:chemistry; D009765:Obesity / Q000150:complications / Q000209:etiology
chemical_list: D016207:Cytokines; D005227:Fatty Acids