title: Are obesity-related insulin resistance and type 2 diabetes autoimmune diseases?
abstract: 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-α 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.
authors.affiliation: Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Sue
authors.initials: S
authors.lastname: Tsai
authors.affiliation: Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Xavier
authors.initials: X
authors.lastname: Clemente-Casares
authors.affiliation: Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Xavier S
authors.initials: XS
authors.lastname: Revelo
authors.affiliation: Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada shawn.winer@utoronto.ca dan.winer@uhn.ca.
authors.forename: Shawn
authors.initials: S
authors.lastname: Winer
authors.affiliation: Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada Department of Pathology, University Health Network, Toronto, Ontario, Canada Division of Endocrinology and Metabolism, Department of Medicine, University Health Network, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada Department of Immunology, University of Toronto, Toronto, Ontario, Canada shawn.winer@utoronto.ca dan.winer@uhn.ca.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Winer
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D009765:Obesity / Q000378:metabolism*