Sleeve Gastrectomy Alters Intestinal Permeability in Diet-Induced Obese Mice.
Claire Blanchard, François Moreau, Julien Chevalier, Audrey Ayer, Damien Garcon, Lucie Arnaud, Jean-Paul Pais de Barros, Thomas Gautier, Michel Neunlist, Bertrand Cariou, Cédric Le May
Author Information
Claire Blanchard: l'Institut du Thorax, INSERM, CNRS, CHU Nantes, University of Nantes, Nantes, France. Claire.blanchard@chu-nantes.fr.
François Moreau: L'institut du Thorax, INSERM-CNRS, University of Nantes, Nantes, France.
Julien Chevalier: INSERM U913, 44093, Nantes, France.
Audrey Ayer: L'institut du Thorax, INSERM-CNRS, University of Nantes, Nantes, France.
Damien Garcon: L'institut du Thorax, INSERM-CNRS, University of Nantes, Nantes, France.
Lucie Arnaud: L'institut du Thorax, INSERM-CNRS, University of Nantes, Nantes, France.
Jean-Paul Pais de Barros: Plateforme de Lipidomique-uBourgogne, INSERM UMR866 / LabEx LipSTIC, Dijon, France.
Thomas Gautier: Plateforme de Lipidomique-uBourgogne, INSERM UMR866 / LabEx LipSTIC, Dijon, France.
Michel Neunlist: INSERM U913, 44093, Nantes, France.
Bertrand Cariou: l'Institut du Thorax, INSERM, CNRS, CHU Nantes, University of Nantes, Nantes, France.
Cédric Le May: L'institut du Thorax, INSERM-CNRS, University of Nantes, Nantes, France.
BACKGROUND: Increased lipopolysaccharide (LPS) translocation due to altered intestinal permeability has been suggested as a mechanism for obesity-associated insulin resistance. The goal of this study was to assess the effect of sleeve gastrectomy (SG) on intestinal barrier permeability in diet-induced obese mice. MATERIALS AND METHODS: Four weeks after surgery, the effects of SG on intestinal permeabilities were assessed ex vivo and in vivo in male C57Bl/6J mice fed a high-fat diet. Gene expression of tight junction proteins and inflammatory cytokines was measured in jejunum, colon, liver, and inguinal adipose tissue. Plasma LPS was quantified by HPLCMS/MS spectrometry. RESULTS: SG significantly reduced body weight and improved glucose homeostasis, as expected. SG decreased paracellular (p = 0.01) and transcellular permeability (p = 0.03) in the jejunum; and increased mRNA levels of the tight junction proteins Jam A (p = 0.02) and occludin (p = 0.01). In contrast in the distal colon, paracellular permeability tended to be increased (p = 0.07) while transcellular permeability was significantly induced (p = 0.03) after SG. In vivo, the paracellular permeability was significantly increased 3 weeks after SG (p = 0.02). Plasma LPS level were increased after SG (p = 0.03), as well as mRNA levels of adipose and hepatic inflammatory markers (p = 0.02). CONCLUSIONS: SG significantly modifies intestinal permeability in a differential manner between the proximal and distal intestine. These changes promote LPS translocation in plasma, induce a low-grade pro-inflammatory state in adipose tissue and liver, but do not impair the SG-induced glucose homeostasis improvement.
