Life sciences · Journal article
Frontiers in Immunology · October 12, 2026
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Postoperative cognitive dysfunction (POCD) is an important complication after surgery, particularly in patients with pre-existing metabolic and inflammatory vulnerability. Obesity may increase susceptibility to postoperative cognitive decline, but its independent association with POCD and the underlying mechanisms remain uncertain. This review critically examines a proposed adipose–immune–brain pathway linking obesity-associated adipose dysfunction to perioperative neurocognitive outcomes. In obesity, adipocyte hypertrophy, hypoxia, fibrosis, macrophage accumulation, T-cell imbalance, and activation of inflammasome and innate immune signaling pathways promote chronic low-grade inflammation and altered endocrine function. The resulting changes in cytokines, adipokines, free fatty acids, lipid mediators, insulin sensitivity, and glucose and lipid metabolism may establish a systemically primed immunometabolic state. Surgical trauma may then act as a second inflammatory hit, amplifying peripheral immune activation and promoting blood–brain barrier dysfunction, glial activation, oxidative stress, and impaired neuronal function. However, direct clinical evidence linking adipose tissue inflammation to POCD remains limited; current support is derived largely from preclinical studies, indirect biomarker associations, and heterogeneous clinical studies that sometimes combine postoperative delirium with longer-term cognitive outcomes. Accordingly, the adipose–immune–brain axis should be regarded as a biologically plausible framework rather than an established causal pathway. Better phenotyping of visceral adiposity and metabolic dysfunction, standardized neurocognitive outcomes, and integrated assessment of adipose, circulating, and blood–brain barrier biomarkers are needed. Potential interventions include weight and metabolic optimization, incretin-based therapies, modulation of inflammatory and pro-resolving pathways, and perioperative physiological management, although their efficacy for preventing POCD remains to be established.