Fig. 1.

Obesity-altered adipocytes promote dysregulated inflammatory responses in infection. Adipocyte-secreted factors (e.g., Adiponectin, Leptin, Type I IFNs, and IL-6) contribute to homeostatic immune responses and appropriate immune defense mechanisms against infectious agents resulting in pathogen clearance in the lean state. Obesity-associated chronic inflammation leads to expansion in adipocyte number and size. These alterations in adipose tissue unlocks a proinflammatory skewing of adipocyte phenotype and leads to dysregulated secretion of adipocyte-produced mediators (increased in red, decreased in blue). Hence, obesity-dependent changes in adipocyte function can contribute to the immune system being in a state of: (1) Immunosenescence (suppressed immune response against pathogens); (2) Delayed immune inflammation (reduced pathogen clearance and compensatory exacerbated adipocyte inflammation); and (3) “Cytokine storm” (uncontrolled proinflammatory response and tissue damage). Overall, each altered inflammatory state in obesity could individually or synergistically shape immune responses, culminating in worsened disease pathology and increased morbidity and mortality.