title: Gastric bypass surgery improves metabolic and hepatic abnormalities associated with nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  Most patients with extreme obesity have nonalcoholic fatty liver disease (NAFLD). Although gastric bypass (GBP) surgery is the most common bariatric operation performed in obese patients in the United States, the effect of GBP surgery-induced weight loss on the metabolic and hepatic abnormalities associated with NAFLD are not clear.
  
  
  METHODS
  Whole-body glucose, fatty acid and lipoprotein kinetics, liver histology, and hepatic cellular factors involved in inflammation and fibrogenesis were evaluated in 7 extremely obese subjects (body mass index, 58 +/- 4 kg/m(2)) before and 1 year after GBP surgery.
  
  
  RESULTS
  At 1 year after surgery, subjects lost 29% +/- 5% of initial body weight (P < .01); palmitate rate of appearance in plasma, an index of adipose tissue lipolysis, decreased by 47% +/- 4% (P < .01); endogenous glucose production rate decreased by 27% +/- 7% (P < .01); and very-low-density lipoprotein-triglyceride secretion rate decreased by 44% +/- 9% (P < .05). In addition, GBP surgery-induced weight loss decreased hepatic steatosis but did not change standard histologic assessments of inflammation and fibrosis. However, there was a marked decrease in hepatic factors involved in regulating fibrogenesis (collagen-alpha1(I), transforming growth factor-beta1, alpha-smooth muscle actin, and tissue inhibitor of metalloproteinase 1 expression and alpha-smooth muscle actin content) and inflammation (macrophage chemoattractant protein 1 and interleukin 8 expression) (P < .05, compared with values before weight loss).
  
  
  CONCLUSIONS
  These data demonstrate that weight loss induced by GBP surgery normalizes the metabolic abnormalities involved in the pathogenesis and pathophysiology of NAFLD and decreases the hepatic expression of factors involved in the progression of liver inflammation and fibrosis.
authors.affiliation: Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA. sklein@im.wustl.edu
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
authors.forename: Bettina
authors.initials: B
authors.lastname: Mittendorfer
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Eagon
authors.forename: Bruce
authors.initials: B
authors.lastname: Patterson
authors.forename: Lafaine
authors.initials: L
authors.lastname: Grant
authors.forename: Nikki
authors.initials: N
authors.lastname: Feirt
authors.forename: Ekihiro
authors.initials: E
authors.lastname: Seki
authors.forename: David
authors.initials: D
authors.lastname: Brenner
authors.forename: Kevin
authors.initials: K
authors.lastname: Korenblat
authors.forename: Jennifer
authors.initials: J
authors.lastname: McCrea
mesh_terms: D000704:Analysis of Variance; D001707:Biopsy, Needle; D001786:Blood Glucose; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D004502:Education, Medical, Continuing; D005227:Fatty Acids / Q000378:metabolism*; D005234:Fatty Liver / Q000150:complications / Q000175:diagnosis*; D005260:Female; D015390:Gastric Bypass / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000502:physiology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000150:complications / Q000175:diagnosis / Q000601:surgery*; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D002784:Cholesterol