Immunometabolic framework links adiposopathy to chronic inflammatory disease, with tirzepatide showing promise in psoriatic arthritis

Beyond its traditional role in energy storage, adipose tissue dysfunction is increasingly recognized as a biologically active contributor to chronic inflammatory disease. In obesity, adiposopathy is characterized by persistent immunometabolic alterations, including adipokine dysregulation, macrophage infiltration, and insulin resistance, leading to chronic low-grade inflammation. These processes intersect with inflammatory signaling pathways central to immune-mediated diseases, creating an immunometabolic phenotype where metabolic dysfunction and immune activation converge to influence disease expression and therapeutic responsiveness.

This review proposes a translational immunometabolic framework by synthesizing existing evidence on adiposopathy and its role in amplifying inflammatory signaling in chronic inflammatory disease. The authors examine how metabolic dysfunction and immune activation intersect to influence disease expression and therapeutic responsiveness. They highlight the recent TOGETHER-PsA trial as a clinical proof-of-concept, demonstrating the potential of targeting adipose tissue dysfunction, specifically with tirzepatide, in conditions like psoriatic arthritis.

The proposed framework posits that adiposopathy is a measurable immunometabolic state that amplifies inflammatory signaling and influences therapeutic responsiveness. This suggests that combined metabolic-immune targeting could be biologically rational in selected patients. The TOGETHER-PsA trial provides a key clinical proof of concept:

Adding tirzepatide to IL-17 inhibition achieved greater disease control than cytokine blockade alone in psoriatic arthritis patients with overweight or obesity. This finding suggests that targeting adipose tissue dysfunction may influence inflammatory disease activity. Furthermore, emerging experimental evidence indicates that incretin-based therapies, including GLP-1 and GIP receptor signaling, may exert direct immunomodulatory effects within immune and myeloid cell populations, extending beyond their weight reduction benefits.