Abstract
IntroductionGut microbiota has been reported to contribute to obesity and the pathology of obesity‐related diseases but the underlying mechanisms are largely unknown. Mucosal‐associated invariant T (MAIT) cells are a unique subpopulation of T cells characterized by the expression of a semi‐invariant T cell receptor (TCR) α chain (Vα19 in mice; Vα7.2 in humans). The expansion and maturation of MAIT cells require the gut microbiota and antigen‐presenting molecule MR1, suggesting that MAIT cells may play a unique role in bridging gut microbiota, obesity, and obesity‐associated inflammation.MethodsThe levels of human MAIT cells from obese patients, as well as mouse MAIT cells from obese mouse models, were determined by flow cytometry. By comparing to controls, we analyzed the change of MAIT cells in obese subjects.ResultsWe found obese patients had fewer circulating MAIT cells than healthy‐weight donors and the difference was more distinct in male patients. Consistently, male mice (but not female mice) have shown reduced MAIT cells in the liver and adipose tissue after a 10‐week Western diet compared to mice on a control diet. We also explored the possibility of utilizing high‐throughput technology (i.e., quantitative polymerase chain reaction [qPCR]), other than flow cytometry, to determine the expression levels of the invariant TCR of human MAIT cells. But a minimal correlation (R 2 = 0.23, p = .11) was observed between qPCR and flow cytometry data.ConclusionOur study suggests that there is a sex discrepancy in the impact of obesity on MAIT cells: MAIT cells in male (but not female) humans and male mice are reduced by obesity.
Highlights
Gut microbiota has been reported to contribute to obesity and the pathology of obesity‐related diseases but the underlying mechanisms are largely unknown
We explored the possibility of utilizing quantitative polymerase chain reaction to measure levels of Vα7.2 T cell receptor (TCR) of Mucosal‐associated invariant T (MAIT) cells in human blood, because qPCR is the gold standard of gene expression quantification and compatible with high‐throughput methods.[22]
MAIT cells from male subjects were inversely correlated with body mass index (BMI) (R2 = 0.2335, p = .09; Figure 1I) but not with age (R2 = 0.035, p = .5424; Figure 1J). These results suggest that obesity reduces the number of circulating MAIT cells and this appears to be more impactful in male obese patients
Summary
The global incidence of obesity has been steadily increasing for the past 10 years.[1,2] According to WHO, over 650 million adults aged 18 years and older, representing 13% of adults worldwide, were obese in 2016.3 Once considered a health problem only in developed countries, obesity has spread to developing countries. Two recent reports demonstrate profound MAIT cell abnormalities in obese patients.[20,21] the impact of sex‐difference on MAIT cells in response to obesity has not been studied. We utilized a Western diet‐ induced obesity (DIO) mouse model to determine how MAIT cells in mice were impacted by increased adiposity. Using flow cytometry, we compared the frequencies of MAIT cells in the peripheral blood between obese patients and healthy donors. We explored the possibility of utilizing quantitative polymerase chain reaction (qPCR) to measure levels of Vα7.2 TCR of MAIT cells in human blood, because qPCR is the gold standard of gene expression quantification and compatible with high‐throughput methods.[22]
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