Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals
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Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals. / Fabbrini, Elisa; Cella, Marina; McCartney, Steve A; Fuchs, Anja; Abumrad, Nada A; Pietka, Terri A; Chen, Zhouji; Finck, Brian N; Han, Dong Ho; Magkos, Faidon; Conte, Caterina; Bradley, David; Fraterrigo, Gemma; Eagon, J Christopher; Patterson, Bruce W; Colonna, Marco; Klein, Samuel.
In: Gastroenterology, Vol. 145, No. 2, 2013, p. 366-374.e1-e3.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals
AU - Fabbrini, Elisa
AU - Cella, Marina
AU - McCartney, Steve A
AU - Fuchs, Anja
AU - Abumrad, Nada A
AU - Pietka, Terri A
AU - Chen, Zhouji
AU - Finck, Brian N
AU - Han, Dong Ho
AU - Magkos, Faidon
AU - Conte, Caterina
AU - Bradley, David
AU - Fraterrigo, Gemma
AU - Eagon, J Christopher
AU - Patterson, Bruce W
AU - Colonna, Marco
AU - Klein, Samuel
N1 - Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
PY - 2013
Y1 - 2013
N2 - Background & aims: An increased number of macrophages in adipose tissue is associated with insulin resistance and metabolic dysfunction in obese people. However, little is known about other immune cells in adipose tissue from obese people, and whether they contribute to insulin resistance. We investigated the characteristics of T cells in adipose tissue from metabolically abnormal insulin-resistant obese (MAO) subjects, metabolically normal insulin-sensitive obese (MNO) subjects, and lean subjects. Insulin sensitivity was determined by using the hyperinsulinemic euglycemic clamp procedure.Methods: We assessed plasma cytokine concentrations and subcutaneous adipose tissue CD4(+) T-cell populations in 9 lean, 12 MNO, and 13 MAO subjects. Skeletal muscle and liver samples were collected from 19 additional obese patients undergoing bariatric surgery to determine the presence of selected cytokine receptors.Results: Adipose tissue from MAO subjects had 3- to 10-fold increases in numbers of CD4(+) T cells that produce interleukin (IL)-22 and IL-17 (a T-helper [Th] 17 and Th22 phenotype) compared with MNO and lean subjects. MAO subjects also had increased plasma concentrations of IL-22 and IL-6. Receptors for IL-17 and IL-22 were expressed in human liver and skeletal muscle samples. IL-17 and IL-22 inhibited uptake of glucose in skeletal muscle isolated from rats and reduced insulin sensitivity in cultured human hepatocytes.Conclusions: Adipose tissue from MAO individuals contains increased numbers of Th17 and Th22 cells, which produce cytokines that cause metabolic dysfunction in liver and muscle in vitro. Additional studies are needed to determine whether these alterations in adipose tissue T cells contribute to the pathogenesis of insulin resistance in obese people.
AB - Background & aims: An increased number of macrophages in adipose tissue is associated with insulin resistance and metabolic dysfunction in obese people. However, little is known about other immune cells in adipose tissue from obese people, and whether they contribute to insulin resistance. We investigated the characteristics of T cells in adipose tissue from metabolically abnormal insulin-resistant obese (MAO) subjects, metabolically normal insulin-sensitive obese (MNO) subjects, and lean subjects. Insulin sensitivity was determined by using the hyperinsulinemic euglycemic clamp procedure.Methods: We assessed plasma cytokine concentrations and subcutaneous adipose tissue CD4(+) T-cell populations in 9 lean, 12 MNO, and 13 MAO subjects. Skeletal muscle and liver samples were collected from 19 additional obese patients undergoing bariatric surgery to determine the presence of selected cytokine receptors.Results: Adipose tissue from MAO subjects had 3- to 10-fold increases in numbers of CD4(+) T cells that produce interleukin (IL)-22 and IL-17 (a T-helper [Th] 17 and Th22 phenotype) compared with MNO and lean subjects. MAO subjects also had increased plasma concentrations of IL-22 and IL-6. Receptors for IL-17 and IL-22 were expressed in human liver and skeletal muscle samples. IL-17 and IL-22 inhibited uptake of glucose in skeletal muscle isolated from rats and reduced insulin sensitivity in cultured human hepatocytes.Conclusions: Adipose tissue from MAO individuals contains increased numbers of Th17 and Th22 cells, which produce cytokines that cause metabolic dysfunction in liver and muscle in vitro. Additional studies are needed to determine whether these alterations in adipose tissue T cells contribute to the pathogenesis of insulin resistance in obese people.
KW - Adult
KW - Animals
KW - Body Mass Index
KW - CD4-Positive T-Lymphocytes/immunology
KW - Case-Control Studies
KW - Cytokines/immunology
KW - Female
KW - Glucose/metabolism
KW - Glucose Clamp Technique
KW - Hepatocytes/drug effects
KW - Humans
KW - Insulin Resistance/immunology
KW - Interleukin-17/metabolism
KW - Interleukin-6/blood
KW - Interleukins/blood
KW - Liver/metabolism
KW - Male
KW - Middle Aged
KW - Muscle, Skeletal/drug effects
KW - Obesity/immunology
KW - Rats
KW - Receptors, Interleukin/metabolism
KW - Receptors, Interleukin-17/metabolism
KW - Subcutaneous Fat/immunology
KW - T-Lymphocyte Subsets/immunology
KW - Th17 Cells/immunology
U2 - 10.1053/j.gastro.2013.04.010
DO - 10.1053/j.gastro.2013.04.010
M3 - Journal article
C2 - 23597726
VL - 145
SP - 366-374.e1-e3
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 2
ER -
ID: 289968349