title: Reduction in endotoxemia, oxidative and inflammatory stress, and insulin resistance after Roux-en-Y gastric bypass surgery in patients with morbid obesity and type 2 diabetes mellitus.
abstract: BACKGROUND
  Roux-en-Y gastric bypass (RYGB) results in profound weight loss and resolution of type 2 diabetes mellitus (T2DM). The mechanism of this remarkable transition remains poorly defined. It has been proposed that endotoxin (lipopolysaccharide [LPS]) sets inflammatory tone, triggers weight gain, and initiates T2DM. Because RYGB may diminish LPS from endogenous and exogenous sources, we hypothesized that LPS and the associated cascade of oxidative and inflammatory stress would diminish after RYGB.
  
  
  METHODS
  Fifteen adults with morbid obesity and T2DM undergoing RYGB were studied. After an overnight fast, a baseline blood sample was collected the morning of surgery and at 180 days to assess changes in glycemia, insulin resistance, LPS, mononuclear cell nuclear factor (NF)-κB binding and mRNA expression of CD14, TLR-2, TLR-4, and markers of inflammatory stress.
  
  
  RESULTS
  At 180 days after RYGB, subjects had a significant decrease in body mass index (52.1 ± 13.0 to 40.4 ± 11.1), plasma glucose (148 ± 8 to 101 ± 4 mg/dL), insulin (18.5 ± 2.2 mμU/mL to 8.6 ± 1.0 mμU/mL) and HOMA-IR (7.1 ± 1.1 to 2.1 ± 0.3). Plasma LPS significantly reduced by 20 ± 5% (0.567 ± 0.033 U/mL to 0.443 ± 0.022 E U/mL). NF-κB DNA binding decreased significantly by 21 ± 8%, whereas TLR-4, TLR-2, and CD-14 expression decreased significantly by 25 ± 9%, 42 ± 8%, and 27 ± 10%, respectively. Inflammatory mediators CRP, MMP-9, and MCP-1 decreased significantly by 47 ± 7% (10.7 ± 1.6 mg/L to 5.8 ± 1.0 mg/L), 15 ± 6% (492 ± 42 ng/mL to 356 ± 26 ng/mL) and 11 ± 4% (522 ± 35 ng/mL to 466 ± 35 ng/mL), respectively.
  
  
  CONCLUSIONS
  LPS, NF-κB DNA binding, TLR-4, TLR-2, and CD14 expression, CRP, MMP-9, and MCP-1 decreased significantly after RYGB. The mechanism underlying resolution of insulin resistance and T2DM after RYGB may be attributable, at least in part, to the reduction of endotoxemia and associated proinflammatory mediators.
authors.affiliation: State University of New York at Buffalo, School of Pharmacy and Pharmaceutical Sciences, Amherst, NY, USA. smonte@cplassociates.com
authors.forename: Scott V
authors.initials: SV
authors.lastname: Monte
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Caruana
authors.forename: Husam
authors.initials: H
authors.lastname: Ghanim
authors.forename: Chang Ling
authors.initials: CL
authors.lastname: Sia
authors.forename: Kelly
authors.initials: K
authors.lastname: Korzeniewski
authors.forename: Jerome J
authors.initials: JJ
authors.lastname: Schentag
authors.forename: Paresh
authors.initials: P
authors.lastname: Dandona
mesh_terms: D000328:Adult; D000886:Anthropometry; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology / Q000601:surgery*; D019446:Endotoxemia / Q000097:blood / Q000150:complications / Q000601:surgery*; D005260:Female; D015390:Gastric Bypass; D006801:Humans; D007249:Inflammation / Q000209:etiology; D007333:Insulin Resistance; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009767:Obesity, Morbid / Q000097:blood / Q000150:complications / Q000276:immunology / Q000601:surgery*; D018384:Oxidative Stress; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4