title: Ileal transposition surgery produces ileal length-dependent changes in food intake, body weight, gut hormones and glucose metabolism in rats.
abstract: BACKGROUND
  Enhanced stimulation of the lower gut is hypothesized to play a key role in the weight loss and resolution of diabetes following bariatric surgeries. Ileal transposition (IT) permits study of the effects of direct lower gut stimulation on body weight, glucose homeostasis and other metabolic adaptations without the confounds of gastric restriction or foregut exclusion. However, the underlying mechanisms and the length of the ileum sufficient to produce metabolic benefits following IT surgery remain largely unknown.
  
  
  OBJECTIVE
  To determine the effects of transposing varying lengths of the ileum to upper jejunum on food intake, body weight, glucose tolerance and lower gut hormones, and the expression of key markers of glucose and lipid metabolism in skeletal muscle and adipose tissue in rats.
  
  
  METHODS
  Adult male Sprague-Dawley rats (n=9/group) were subjected to IT surgery with translocation of 5, 10 or 20 cm of the ileal segment to proximal jejunum or sham manipulations. Daily food intake and body weight were recorded, and an intraperitoneal glucose tolerance test was performed. Blood samples were assayed for hormones and tissue samples for mRNA (RT-qPCR) and/or protein abundance (immunoblotting) of regulatory metabolic markers.
  
  
  RESULTS
  We demonstrate that IT surgery exerts ileal length-dependent effects on multiple parameters including: (1) decreased food intake and weight gain, (2) improved glucose tolerance, (3) increased tissue expression and plasma concentrations of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), and decreased leptin concentrations and (4) upregulation of key markers of glucose metabolism (glucose transporter-4 (GLUT-4), insulin receptor substrate 1 (IRS-1), adenosine monophosphate-activated protein kinase (AMPK), hexokinase (HK) and phosphofructokinase (PFK)) together with a downregulation of lipogenic markers (fatty acid synthase (FAS)) in muscle and adipose tissue.
  
  
  CONCLUSIONS
  Together, our data demonstrate that the reduction in food intake and weight gain, increase in lower gut hormones, glycemic improvements and associated changes in tissue metabolic markers following IT surgery are dependent on the length of the transposed ileum.
authors.affiliation: Department of Production Animal Health, Faculty of Veterinary Medicine, Alberta, Calgary, Canada.
authors.forename: A R
authors.initials: AR
authors.lastname: Ramzy
authors.affiliation: Department of Production Animal Health, Faculty of Veterinary Medicine, Alberta, Calgary, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Nausheen
authors.affiliation: 1] Department of Production Animal Health, Faculty of Veterinary Medicine, Alberta, Calgary, Canada [2] Gastrointestinal Research Group, Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Calgary, Canada.
authors.forename: P K
authors.initials: PK
authors.lastname: Chelikani
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating; D005743:Gastrectomy; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006706:Homeostasis; D007082:Ileum / Q000378:metabolism / Q000601:surgery*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D019894:Peptide YY / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D005768:Gastrointestinal Hormones; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D020738:Leptin; C495694:Slc2a4 protein, rat; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1; D055372:AMP-Activated Protein Kinases