Immunometabolic Dysregulation in Obesity: Integrating Macrophage Polarization, Metabolic Reprogramming, and Gut Microbiota Crosstalk.

BACKGROUND

Obesity is characterized by chronic low-grade systemic inflammation, in which adipose tissue macrophages (ATMs) play a pivotal role in driving immune and metabolic dysfunction.

OBJECTIVE

This review summarizes current evidence on the roles of ATMs in obese adipose tissue and examines how macrophage polarization and metabolic reprogramming are linked to fatty acid metabolism, insulin resistance (IR), and gut microbiota dysbiosis.

RECENT FINDINGS: Previous studies have often addressed macrophage dysfunction, fatty acid metabolism, IR, and gut microbiota alterations as separate processes. In contrast, this review integrates these obesity-related events within a unified immunometabolic framework centered on ATMs. Obesity induces marked phenotypic shifts and metabolic reprogramming in ATMs, thereby promoting chronic inflammation and IR. Disturbed fatty acid metabolism and gut microbiota dysbiosis further impair metabolic homeostasis and intestinal barrier integrity, reinforcing a vicious cycle of macrophage-driven immunometabolic dysfunction.

CONCLUSIONS

This review highlights the central role of ATM-mediated immune-metabolic crosstalk in obesity and emphasizes the therapeutic potential of targeting macrophage dysfunction and gut microbiota alterations to attenuate obesity-related metabolic complications.