Triggering receptor expressed on myeloid cells 2-driven pancreatic macrophage crosstalk: Key regulator of obesity pathophysiology and metabolic dysregulation

Figure 1 Schematic diagram of TREM2-driven pancreatic macrophage activation in obesity and its metabolic consequences. Triggering receptor expressed on myeloid cells 2 (TREM2) is markedly upregulated in pancreatic macrophages during obesity, reprogramming them to a pro-inflammatory state. This TREM2-driven activation disrupts the crosstalk with islet β-cells, leading to local insulin resistance and metabolic imbalance. Crucially, as the figure depicts, genetic ablation of TREM2 reprograms macrophages to a resting (TREM2^-) phenotype. This intervention attenuates inflammation, restores β-cell function and insulin secretion, and re-establishes systemic metabolic homeostasis, validating TREM2 as a pivotal molecular switch and a promising therapeutic target. TREM2: Triggering receptor expressed on myeloid cells 2.