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Cell Metab. 2015 Jul 7;22(1):113-24. doi: 10.1016/j.cmet.2015.05.020. Epub 2015 Jun 18.

Jejunal T Cell Inflammation in Human Obesity Correlates with Decreased Enterocyte Insulin Signaling.

Author information

1
Sorbonne Universités, UPMC Univ Paris 06, UMRS 1138 and UMRS 1166, F-75005 Paris, France; INSERM, UMRS 1138, Centre de Recherche des Cordeliers, F-75005 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière Hospital F-75013, Paris, France.
2
Sorbonne Universités, UPMC Univ Paris 06, UMRS 1138 and UMRS 1166, F-75005 Paris, France; INSERM, UMRS 1166, Nutriomics team 6, F-75013 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière Hospital F-75013, Paris, France.
3
INSERM, UMRS 1166, Nutriomics team 6, F-75013 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière Hospital F-75013, Paris, France.
4
Sorbonne Universités, UPMC Univ Paris 06, UMRS 1138 and UMRS 1166, F-75005 Paris, France; INSERM, UMRS 1166, Nutriomics team 6, F-75013 Paris, France; Assistance Publique Hôpitaux de Paris, AP-HP, Pitié Salpêtrière hospital, Nutrition and Endocrinology Department and Hepato-biliary and Digestive Surgery Department, F-75013 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière Hospital F-75013, Paris, France.
5
Sorbonne Universités, UPMC Univ Paris 06, UMRS 1138 and UMRS 1166, F-75005 Paris, France; INSERM, UMRS 1138, Centre de Recherche des Cordeliers, F-75005 Paris, France.
6
INSERM, UMRS 1138, Centre de Recherche des Cordeliers, F-75005 Paris, France; Université Paris Descartes-Paris 5, UMRS 1138, F-75006 Paris, France.
7
Sorbonne Universités, UPMC Univ Paris 06, UMRS 1138 and UMRS 1166, F-75005 Paris, France; INSERM, UMRS 1166, Nutriomics team 6, F-75013 Paris, France; Assistance Publique Hôpitaux de Paris, AP-HP, Pitié Salpêtrière hospital, Nutrition and Endocrinology Department and Hepato-biliary and Digestive Surgery Department, F-75013 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière Hospital F-75013, Paris, France. Electronic address: karine.clement@psl.aphp.fr.
8
Sorbonne Universités, UPMC Univ Paris 06, UMRS 1138 and UMRS 1166, F-75005 Paris, France; INSERM, UMRS 1138, Centre de Recherche des Cordeliers, F-75005 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière Hospital F-75013, Paris, France. Electronic address: edith.brot-laroche@crc.jussieu.fr.

Abstract

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.

PMID:
26094890
DOI:
10.1016/j.cmet.2015.05.020
[Indexed for MEDLINE]
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