Sleeve Gastrectomy Alters Intestinal Permeability in Diet-Induced Obese Mice

Obes Surg. 2017 Oct;27(10):2590-2598. doi: 10.1007/s11695-017-2670-1.

Abstract

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.

Keywords: Glucose homeostasis; Inflammation; Intestinal permeability; LPS; Sleeve gastrectomy.

MeSH terms

  • Adipose Tissue / metabolism
  • Adiposity
  • Animals
  • Diet, High-Fat*
  • Gastrectomy / methods
  • Insulin Resistance
  • Intestinal Mucosa / metabolism*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / etiology
  • Obesity / surgery*
  • Permeability