title: Jejunal T Cell Inflammation in Human Obesity Correlates with Decreased Enterocyte Insulin Signaling.
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.
authors.affiliation: 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.
authors.forename: Milena
authors.initials: M
authors.lastname: Monteiro-Sepulveda
authors.affiliation: 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.
authors.forename: Sothea
authors.initials: S
authors.lastname: Touch
authors.affiliation: INSERM, UMRS 1166, Nutriomics team 6, F-75013 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière Hospital F-75013, Paris, France.
authors.forename: Carla
authors.initials: C
authors.lastname: Mendes-Sá
authors.affiliation: 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.
authors.forename: Sébastien
authors.initials: S
authors.lastname: André
authors.affiliation: 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.
authors.forename: Christine
authors.initials: C
authors.lastname: Poitou
authors.affiliation: 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.
authors.forename: Omran
authors.initials: O
authors.lastname: Allatif
authors.affiliation: 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.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cotillard
authors.affiliation: 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.
authors.forename: Hélène
authors.initials: H
authors.lastname: Fohrer-Ting
authors.affiliation: 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.
authors.forename: Edwige-Ludiwyne
authors.initials: EL
authors.lastname: Hubert
authors.affiliation: INSERM, UMRS 1138, Centre de Recherche des Cordeliers, F-75005 Paris, France; Université Paris Descartes-Paris 5, UMRS 1138, F-75006 Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Remark
authors.affiliation: 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.
authors.forename: Laurent
authors.initials: L
authors.lastname: Genser
authors.affiliation: 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.
authors.forename: Joan
authors.initials: J
authors.lastname: Tordjman
authors.affiliation: 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.
authors.forename: Kevin
authors.initials: K
authors.lastname: Garbin
authors.affiliation: 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.
authors.forename: Céline
authors.initials: C
authors.lastname: Osinski
authors.affiliation: INSERM, UMRS 1138, Centre de Recherche des Cordeliers, F-75005 Paris, France; Université Paris Descartes-Paris 5, UMRS 1138, F-75006 Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
authors.affiliation: 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.
authors.forename: Armelle
authors.initials: A
authors.lastname: Leturque
authors.affiliation: 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.
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.affiliation: 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.
authors.forename: Edith
authors.initials: E
authors.lastname: Brot-Laroche
mesh_terms: D000328:Adult; D016827:CD8 Antigens / Q000276:immunology; D002478:Cells, Cultured; D020895:Enterocytes / Q000276:immunology / Q000473:pathology*; D005260:Female; D051273:Glucose Transporter Type 2 / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000276:immunology / Q000473:pathology; D007328:Insulin / Q000276:immunology*; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007583:Jejunum / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*
chemical_list: D016827:CD8 Antigens; C433839:CD8alphabeta antigen; D051273:Glucose Transporter Type 2; D007328:Insulin; C495680:SLC2A2 protein, human