Obesity and associated insulin resistance predispose individuals to develop chronic metabolic diseases, such as type 2 diabetes and cardiovascular disease. Although these disorders affect a significant proportion of the global population, the underlying mechanisms of disease remain poorly understood. The discovery of elevated tumor necrosis factor- A in adipose tissue as an inducer of obesity- Associated insulin resistance marked a new era of understanding that a subclinical inflammatory process underlies the insulin resistance and metabolic dysfunction that precedes type 2 diabetes. Advances in the field identified components of both the innate and adaptive immune response as key players in regulating such inflammatory processes. As antigen specificity is a hallmark of an adaptive immune response, its role in modulating the chronic inflammation that accompanies obesity and type 2 diabetes begs the question of whether insulin resistance and type 2 diabetes can have autoimmune components. In this Perspective, we summarize current data that pertain to the activation and perpetuation of adaptive immune responses during obesity and discuss key missing links and potential mechanisms for obesity-related insulin resistance and type 2 diabetes to be considered as potential autoimmune diseases.
Bibliographical noteFunding Information:
Funding. Studies of obesity-associated adaptive immune responses in the laboratory of the authors were supported in part by Canadian Institutes of Health Research grant 119414 (D.A.W.), Canadian Diabetes Association grants OG-3-12-3844 and CS-5-12-3886 (D.A.W.), and the University of Toronto Banting & Best Diabetes Centre Sun Life New Investigator Award (D.A.W.). S.T. is a recipient of a Canadian Institutes of Health Research Banting Postdoctoral Fellowship. X.S.R. is the recipient of a Banting & Best Diabetes Centre Fellowship in Diabetes Care (funded by Eli Lilly Canada). Duality of Interest. No potential conflicts of interest relevant to this article were reported.