title: Altered intestinal functions and increased local inflammation in insulin-resistant obese subjects: a gene-expression profile analysis.
abstract: BACKGROUND
  Metabolic alterations relevant to postprandial dyslipidemia were previously identified in the intestine of obese insulin-resistant subjects. The aim of the study was to identify the genes deregulated by systemic insulin resistance in the intestine of severely obese subjects.
  
  
  METHODS
  Transcripts from duodenal samples of insulin-sensitive (HOMA-IR < 3, n = 9) and insulin-resistant (HOMA-IR > 7, n = 9) obese subjects were assayed by microarray (Illumina HumanHT-12).
  
  
  RESULTS
  A total of 195 annotated genes were identified as differentially expressed between these two groups (Fold change > 1.2). Of these genes, 36 were found to be directly involved in known intestinal functions, including digestion, extracellular matrix, endocrine system, immunity and cholesterol metabolism. Interestingly, all differentially expressed genes (n = 8) implicated in inflammation and oxidative stress were found to be upregulated in the intestine of insulin-resistant compared to insulin-sensitive subjects. Metabolic pathway analysis revealed that several signaling pathways involved in immunity and inflammation were significantly enriched in differently expressed genes and were predicted to be activated in the intestine of insulin-resistant subjects. Using stringent criteria (Fold change > 1.5; FDR < 0.05), three genes were found to be significantly and differently expressed in the intestine of insulin-resistant compared to insulin-sensitive subjects: the transcripts of the insulinotropic glucose-dependant peptide (GIP) and of the β-microseminoprotein (MSMB) were significantly reduced, but that of the humanin like-1 (MTRNR2L1) was significantly increased.
  
  
  CONCLUSIONS
  These results underline that systemic insulin resistance is associated with remodeling of key intestinal functions. Moreover, these data indicate that small intestine metabolic dysfunction is accompanied with a local amplification of low-grade inflammatory process implicating several pathways. Genes identified in this study are potentially triggered throughout the development of intestinal metabolic abnormalities, which could contribute to dyslipidemia, a component of metabolic syndrome and diabetes.
authors.affiliation: Department of Nutrition, Université de Montréal and Research center of CHU Sainte-Justine, 3175 Côte Ste-Catherine, Montréal, Qc, Canada. alain.veilleux@fsaa.ulaval.ca.
authors.forename: Alain
authors.initials: A
authors.lastname: Veilleux
authors.affiliation: Department of Nutrition, Université de Montréal and Research center of CHU Sainte-Justine, 3175 Côte Ste-Catherine, Montréal, Qc, Canada. sylvainmayeur@yahoo.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mayeur
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Québec, Qc, Canada. jean-christophe.berube@criucpq.ulaval.ca.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Bérubé
authors.affiliation: Departement of Anatomy and cellular biology, Université de Sherbrooke, Sherbrooke, Qc, Canada. Jean-Francois.Beaulieu@usherbrooke.ca.|Canada Research Chair in Intestinal Physiopathology, Sherbrooke, Québec, Canada. Jean-Francois.Beaulieu@usherbrooke.ca.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Beaulieu
authors.affiliation: Departement of Anatomy and cellular biology, Université de Sherbrooke, Sherbrooke, Qc, Canada. Eric.Tremblay@usherbrooke.ca.
authors.forename: Eric
authors.initials: E
authors.lastname: Tremblay
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Québec, Qc, Canada. frederic.hould@chg.ulaval.ca.|Departement of surgery, Université Laval, Québec, Qc, Canada. frederic.hould@chg.ulaval.ca.
authors.forename: Frédéric-Simon
authors.initials: FS
authors.lastname: Hould
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Québec, Qc, Canada. yohan.bosse@criucpq.ulaval.ca.|Department of Molecular Medicine, Université Laval, Quebec, Qc, Canada. yohan.bosse@criucpq.ulaval.ca.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Québec, Qc, Canada. Denis.Richard@criucpq.ulaval.ca.|Department of Molecular Medicine, Université Laval, Quebec, Qc, Canada. Denis.Richard@criucpq.ulaval.ca.|Chaire de Recherche Merck Frosst/IRSC Research Chair on Obesity, Québec, Qc, Canada. Denis.Richard@criucpq.ulaval.ca.
authors.forename: Denis
authors.initials: D
authors.lastname: Richard
authors.affiliation: Department of Nutrition, Université de Montréal and Research center of CHU Sainte-Justine, 3175 Côte Ste-Catherine, Montréal, Qc, Canada. emile.levy@recherche-ste-justine.qc.ca.|JA. deSève Research Chair in nutrition, Montréal, Qc, Canada. emile.levy@recherche-ste-justine.qc.ca.
authors.forename: Emile
authors.initials: E
authors.lastname: Levy
mesh_terms: D000328:Adult; D018938:Caco-2 Cells; D004386:Duodenum; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D046228:Microarray Analysis; D009765:Obesity / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D018384:Oxidative Stress / Q000235:genetics; D029584:Prostatic Secretory Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C000607374:MTRNR2L1 protein, human; D029584:Prostatic Secretory Proteins; D011506:Proteins; D012333:RNA, Messenger; C043076:beta-microseminoprotein; D005749:Gastric Inhibitory Polypeptide