Fig. 3

A vicious cycle of immune dysregulation during obesity and aging mediated by autoantibodies. During obesity and aging, the generation of autoantibodies depends on various interconnecting mechanisms, including ones that directly contribute to alteration in B cell functions and antibody structures, as well as several hallmarks of aging that promote the formation of autoantigens. The autoantibodies then play a critical role in fueling chronic inflammation that eventually contributes to immunosenescence, which continues to drive age-related diseases and metabolic syndromes. While obesity-related autoantibodies can contribute to metabolic syndromes, and age-related autoantibodies can contribute to age-related diseases (denoted as solid arrows), metabolic syndromes and age-related diseases can potentially create niches for the generation of age-related and obesity-related autoantibodies, respectively (denoted as dashed arrows). As a result, a vicious cycle between metabolic syndromes and age-related diseases forms and can exacerbate each other when driven by immunosenescence and chronic inflammation associated with autoantibodies. AGE = Advanced glycation end product; DAMPs = Danger-associated molecular patterns; PAMPs = Pathogen-associated molecular patterns; HFD = High-fat diet; SHM = Somatic hypermutation