Association Between Specific Adipose Tissue CD4+ T-Cell Populations and Insulin Resistance in Obese Individuals

Abstract

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.

Altered Distribution and Increased IL-17 Production by Mucosal-Associated Invariant T Cells in Adult and Childhood Obesity

“…These data are supported by a recent study by Magalhaes et al (18), who also report alteration in MAIT cell frequency and function in obese adults with T2DM. IL-17 signature cytokines have been shown to induce insulin resistance in adipocytes, skeletal muscle cells, and hepatocytes (25)(26)(27). Our demonstration that MAIT cells from obese subjects are significant producers of IL-17 may represent another mechanistic link between obesity and insulin resistance.…”

“…The reduction in IL-10-producing MAIT cells and an increase in the frequency of IL-17-producing MAIT cells in obese AT further supports the concept of an alternatively activated MAIT cell in obesity. Again, the alternative activation of MAIT cells in AT may contribute to morbidity, because increased IL-17 production in AT has been linked to insulin resistance in adipocytes, hepatocytes, and muscle cells (25,26).…”

Immune Cell Crosstalk in Obesity: A Key Role for Costimulation?

“…Of note, the visceral AT Tregs are of a special phenotype, with peroxisome proliferator-activated receptor g as the major orchestrator of Treg accumulation, phenotype, and function (19). The other T-cell subset proven to promote IR is Th17, which is increased 3-to 10-fold in obese subjects and which reduces glucose uptake in skeletal muscle (20). Natural killer T (NKT) cells are a special subset of T cells and have characteristics of both adaptive and innate immune cells.…”

Роль Імунної Системи У Механізмі Терапевтичної Дії Метформіну У Хворих На Цукровий Діабет 2-Го Типу

“…an increase in the CD4 + T cell count in BP of the examined patients with T2D, which is also observed in MS and IR, as well as in normoglycemic obese individuals [12,36,39]. And weight loss as a result of diet or surgical removal of FT excess, the content of this subpopulation of T-lymphocytes in BP decreases [27].…”

“…+ FOXp3 + cells, whose number in obesity in visceral FT can be increased by almost 10 times [12,36].…”