Abstract
Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor whose transcription activity is regulated by small compounds provided by diet, xenobiotics, and metabolism. It has been proven to be involved in energy homeostasis and inflammation in most recent years. Epidemiologically, exposure to xenobiotic AHR ligands contributes to obesity and type 2 diabetes (T2D). AHR is also the critical transcription factor determining the lineage commitment of pro-inflammatory Th17 and Th22 cells from naïve CD4+ T lymphocytes. It has been well-illustrated in animal models that IL-22, the major effector cytokine of Th17 and Th22 cells, played a major role in the interaction of metabolism and gut microbiota. But there were still missing links between gut microbiota, IL-22, and metabolism in humans. Our previous findings indicated that elevated circulating levels of IL-22 and frequencies of Th22 cells were associated with insulin resistance in both patients with obesity and T2D. Additionally, the hyperactive Th17 and Th22 cells phenotype also correlate with islets β-cell dysfunction in T2D. In this study, we made efforts to determine AHR expressions in peripheral blood mononuclear cells (PBMCs) from patients with T2D and metabolically healthy obesity (MHO). Correlation analyses were conducted to assess the possible link between AHR and the metabolic and inflammatory context. We revealed that mRNA expression of AHR was up-regulated and correlated with the percentage of Th17, Th22 as well as Th1 cells. Elevated plasma levels of IL-22 and IL-17 also correlated with increased AHR transcripts in PBMCs from both MHO and T2D patients. The transcription factor AHR may thus have a plausible role in the interaction between metabolism and pro-inflammatory status of patients in the development of obesity and T2D.
Highlights
The prevalence of obesity, in parallel with type 2 diabetes (T2D), has expanded immensely in recent years and has risen as a global epidemic concern [1]
We did not observe significantly higher fasting glucose in metabolically healthy obesity (MHO) participants, there were significant elevations in Ln (HOMA-IR) and serum levels of leptin, insulin, TNFα, IL-22, and hypersensitive Creactive protein (hsCRP) compared with CTLs
Ln (HOMA-IR) and serum levels of IL-17, IL-22 were even significantly higher in T2D patients compared with the MHO group, indicating a decompensating inflammatory status
Summary
The prevalence of obesity, in parallel with type 2 diabetes (T2D), has expanded immensely in recent years and has risen as a global epidemic concern [1]. Previous works revealed that T cell subsets were important regulators of meta-inflammation in both animal models and patients with obesity and T2D [7]. These studies identified an significant elevation in the Th17 and Th1 subsets together with a decrease in the Treg subset [3, 4]. The notable correlation of pro-inflammatory Th subsets with clinical parameters in patients implicate that the immunologic disturbance may play more determinant roles in both insulin resistance and β-cells dysfunction [9, 12,13,14]. Up until recently, the specific immunologic sensors involved in response to metabolic stress to produce such a state of immunologic disturbance were not identified
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