Immunometabolic crosstalk between dysfunctional adipose tissue and the brain: implications for postoperative...

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.