Editors' ChoiceINSULIN RESISTANCE

T-rains Derailed in Fat Depots Cause Insulin Resistance

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Science Translational Medicine  10 Dec 2014:
Vol. 6, Issue 266, pp. 266ec210
DOI: 10.1126/scitranslmed.aaa3456

Increasing rates of obesity are putting an enormous number of individuals at a greater risk of diabetes, but how obesity leads to diabetes remains elusive. In mice, obesity promotes residence of proinflammatory T lymphocytes in adipose tissues, which in turn contributes to insulin resistance. To see if this scenario applies in obese humans, McLaughlin et al. tested whether the T cells in adipose tissue were related to local and systemic inflammation and to glucose metabolism. Their results established a robust connection of proinflammatory T cell balance in human adipose tissues to inflammation and insulin resistance.

McLaughlin et al. recruited nondiabetic overweight and obese volunteers and individuals undergoing gastric bypass surgery. They characterized the T cells in their visceral and subcutaneous adipose tissue by flow cytometry and real-time polymerase chain reaction (RT-PCR), and tested local and systemic inflammation as well as glucose concentrations. CD4 and CD8 T cells were found in both fat depots, but proinflammatory T helper 1(Th1), Th17 and CD8 T cells were more frequent in visceral fat, and the proinflammatory cytokines interleukin-6 (IL-6) and IL-17 were expressed more highly in visceral than in subcutaneous fat. In contrast, the anti-inflammatory cytokine IL-10 was decreased in visceral compared with subcutaneous fat. Last, Th2 cell frequency at both sites of fat deposition was negatively correlated with plasma glucose concentrations. The investigators concluded that there is compelling evidence for an association of the adaptive immune system with systemic inflammation and insulin resistance in overweight and obese humans.

The study has limitations, including a small sample size and correlational design, but is strengthened by the parallel analysis of visceral and subcutaneous fat in people at increased risk of diabetes. These results suggest that T cells may hold the key for the prevention of diabetes due to obesity.

T. McLaughlin et al., T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans. Arterioscler. Thromb. Vasc. Biol. 34, 2637–2643 (2014). [Abstract]

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