Published: 02 July 2015
- Human obesity causes an increase in the jejunal mucosal surface
- Both innate and adaptive immune cells are increased in the gut in obesity
- There is increased homing of CD8αβ T cells in the obese jejunum epithelium
- T cells from obese subjects impair insulin sensitivity of enterocyte
In obesity, insulin resistance is linked to inflammation in several tissues. Although the gut is a very large lymphoid tissue, inflammation in the absorptive small intestine, the jejunum, where insulin regulates lipid and sugar absorption is unknown. We analyzed jejunal samples of 185 obese subjects stratified in three metabolic groups: without comorbidity, suffering from obesity-related comorbidity, and diabetic, versus 33 lean controls. Obesity increased both mucosa surface due to lower cell apoptosis and innate and adaptive immune cell populations. The preferential CD8αβ T cell location in epithelium over lamina propria appears a hallmark of obesity. Cytokine secretion by T cells from obese, but not lean, subjects blunted insulin signaling in enterocytes relevant to apical GLUT2 mislocation. Statistical links between T cell densities and BMI, NAFLD, or lipid metabolism suggest tissue crosstalk. Obesity triggers T-cell-mediated inflammation and enterocyte insulin resistance in the jejunum with potential broader systemic implications.
Milena Monteiro-Sepulveda, Sothea Touch, Carla Mendes-Sá, Sébastien André, Christine Poitou, Omran Allatif, Aurélie Cotillard, Hélène Fohrer-Ting, Edwige-Ludiwyne Hubert, Romain Remark, Laurent Genser, Joan Tordjman, Kevin Garbin, Céline Osinski, Catherine Sautès-Fridman, Armelle Leturque, Karine Clément, Edith Brot-Laroche