Disrupting the adiposopathy-inflammation loop: a translational immunometabolic framework for inflammatory disease.

Adipose tissue dysfunction is increasingly recognized as a biologically active contributor to chronic inflammatory disease beyond its traditional role in energy storage. In the context of obesity, adiposopathy is characterized by persistent immunometabolic alterations involving adipokine dysregulation, macrophage infiltration, insulin resistance, and chronic low-grade inflammation. These processes intersect with inflammatory signaling pathways central to immune-mediated diseases, supporting the concept of an immunometabolic phenotype in which metabolic dysfunction and immune activation converge to influence disease expression and therapeutic responsiveness. This framework does not merely restate the association between obesity and inflammation; rather, it proposes adiposopathy as a measurable immunometabolic state that may amplify inflammatory signaling, influence therapeutic responsiveness, and identify patients in whom combined metabolic-immune targeting could be biologically rational. The recent TOGETHER-PsA trial provides an important clinical proof of concept for this framework, demonstrating that adding tirzepatide to IL-17 inhibition achieved greater disease control than cytokine blockade alone in psoriatic arthritis among those with overweight or obesity. Rather than representing definitive evidence of disease modification, these findings suggest that targeting adipose tissue dysfunction may influence inflammatory disease activity in selected contexts. Extrapolation from this single, disease-specific trial should therefore be regarded as hypothesis-generating and requires validation in other inflammatory conditions. Emerging evidence further indicates that incretin-based therapies may exert anti-inflammatory effects extending beyond weight reduction alone. Experimental studies support potential direct immunomodulatory roles of GLP-1 and GIP receptor signaling within immune and myeloid cell populations, although the relative contribution of direct receptor-mediated pathways versus secondary metabolic improvement remains incompletely understood. Within this emerging translational framework, adiposopathy may represent a therapeutically actionable upstream regulator of inflammatory signaling. Further mechanistic and clinical studies are needed to clarify how modulation of adipose tissue dysfunction may complement conventional immune-targeted therapies across chronic inflammatory diseases.