Sleeve Gastrectomy Alters Intestinal Permeability in Diet-Induced Obese Mice.

Abstract

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. 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. 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 3weeks 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). 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.