The impact of adiposity on adipose tissue-resident lymphocyte activation in humans

Abstract

Background/objectives:The presence of T lymphocytes in human adipose tissue has only recently been demonstrated and relatively little is known of their potential relevance in the development of obesity-related diseases. We aimed to further characterise these cells and in particular to investigate how they interact with modestly increased levels of adiposity typical of common overweight and obesity.Subjects/methods:Subcutaneous adipose tissue and fasting blood samples were obtained from healthy males aged 35–55 years with waist circumferences in lean (<94 cm), overweight (94–102 cm) and obese (>102 cm) categories. Adipose tissue-resident CD4+ and CD8+ T lymphocytes together with macrophages were identified by gene expression and flow cytometry. T lymphocytes were further characterised by their expression of activation markers CD25 and CD69. Adipose tissue inflammation was investigated using gene expression analysis and tissue culture.Results:Participants reflected a range of adiposity from lean to class I obesity. Expression of CD4 (T-helper cells) and CD68 (macrophage), as well as FOXP3 RNA transcripts, was elevated in subcutaneous adipose tissue with increased levels of adiposity (P<0.001, P<0.001 and P=0.018, respectively). Flow cytometry revealed significant correlations between waist circumference and levels of CD25 and CD69 expression per cell on activated adipose tissue-resident CD4+ and CD8+ T lymphocytes (P-values ranging from 0.053 to <0.001). No such relationships were found with blood T lymphocytes. This increased T lymphocyte activation was related to increased expression and secretion of various pro- and anti-inflammatory cytokines from subcutaneous whole adipose tissue explants.Conclusions:This is the first study to demonstrate that even modest levels of overweight/obesity elicit modifications in adipose tissue immune function. Our results underscore the importance of T lymphocytes during adipose tissue expansion, and the presence of potential compensatory mechanisms that may work to counteract adipose tissue inflammation, possibly through an increased number of T-regulatory cells.

Increased fat cell size: a major phenotype of subcutaneous white adipose tissue in non-obese individuals with type 2 diabetes

“…Furthermore, correlations between the M1/M2 macrophage ratio and TNF-α secretion as well as with glycerol release suggest that a switch of the macrophage phenotype towards M1 proinflammatory macrophages might contribute to the development of an unfavourable insulin-resistant metabolic phenotype in non-obese WAT in a similar way to that reported for obese WAT [3,4,[32][33][34]. An increase in the T cell populations in WAT, as well as inflammatory T cell predominance in the circulation, has been associated with obesity [35][36][37]. In contrast to previous reports in obesity, the major T cell populations (CD4 + and CD8 + ) did not associate with any of the adipose tissue phenotypes in our non-obese participants.…”

Interaction between human mature adipocytes and lymphocytes induces T-cell proliferation

“…Finally, in line with data showed here adipose tissueeresident lymphocytes showed a high expression of LEPR. Travers et al [17] demonstrated that modest adipose tissue expansion was characterized not by an increase in the proportion of activated T lymphocytes but rather by a stronger state of activation in the T lymphocytes already expressing CD69 and/or CD25 and this increased activation was not observed in circulating blood T lymphocytes.…”

Gene expression profile of subcutaneous adipose tissue in BMI-discordant monozygotic twin pairs unravels molecular and clinical changes associated with sub-types of obesity

“…49 Alternatively, lymphocytes may precede macrophage infiltration in obese AT presenting an early inflammatory stage that may itself modify the number and the activation state of AT macrophages. [50][51][52][53] It is also possible that the true inflammatory response of AT involves a complex mixture of cell types and cellular events, as has been seen in other recent obesity studies.…”