title: Roux-en-Y gastric bypass improves glucose homeostasis, reduces oxidative stress and inflammation in livers of obese rats and in Kupffer cells via an AMPK-dependent pathway.
abstract: Oxidative stress and inflammation are implicated in the pathogenesis of steatohepatitis. We hypothesize that Roux-en-Y gastric bypass reduces oxidative stress and inflammation in the liver of obese rats via activation of AMPK-α.
  
  
  
  Obese Sprague-Dawley male rats underwent either sham operation or Roux-en-Y gastric bypass. Hepatic TNF-α, NF-κB, IRS-2, PI3 kinase, PKC-ζ, NOX2, and AMPK-α were measured. Mechanistic studies were done in a rat Kupffer cell line (RKC1) that was treated with free fatty acids to mimic lipotoxicity and then transfected with AMPK-α siRNA. Reactive oxygen species, TNF-α, NF-κB, AMPK-α, p-AMPK-α, PPAR-γ, and NOX2 were measured. A t test was used.
  
  
  
  Roux-en-Y gastric bypass lowered nonfasting serum glucose, improved the glucose tolerance test, and induced IRS2/PI3 kinase interaction. Additionally, Roux-en-Y gastric bypass decreased hepatic NOX2, PKC-ζ, TNF-α expression and activation of NF-κB. Free fatty acids increased reactive oxygen species, TNF-α protein, NOX2 protein, and activated NF-κB. Rosiglitazone attenuated the free fatty acids-induced increase in reactive oxygen species, TNF-α, NOX2, and NF-κB; blocking AMPK-α by siRNA abolished the effects of rosiglitazone.
  
  
  
  Roux-en-Y gastric bypass exhibits antidiabetic properties and is associated with downregulation of proinflammation genes and oxidative stress in the liver and within Kupffer cells via activation of AMPK-α.
authors.affiliation: Department of Surgery, University of South Florida, Tampa, FL.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Surgery, University of South Florida, Tampa, FL.
authors.forename: James Zongyu
authors.initials: JZ
authors.lastname: Li
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL.
authors.forename: Min
authors.initials: M
authors.lastname: You
authors.affiliation: Department of Surgery, University of South Florida, Tampa, FL; Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL. Electronic address: mmurr@health.usf.edu.
authors.forename: Michel M
authors.initials: MM
authors.lastname: Murr
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D015390:Gastric Bypass; D007728:Kupffer Cells; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D055372:AMP-Activated Protein Kinases