TREM2 as a Regulator of Obesity-Induced Cardiac Remodeling: Mechanisms and Therapeutic Insights.

Obesity and type 2 diabetes mellitus (T2DM) are global health challenges that significantly increase the risk of cardiovascular diseases (CVD). Advances in immunometabolism have identified Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) as a key regulator of macrophage function, lipid metabolism, and inflammation resolution. While extensively studied in neurodegenerative diseases, TREM2's role in metabolic disorders and cardiovascular health is an emerging area of research. This review explores TREM2's molecular structure and functions, emphasizing its contributions to immunometabolic regulation in obesity and T2DM. Evidence from preclinical models demonstrates that TREM2 modulates macrophage-driven inflammatory responses, lipid clearance, plaque stability, fibrosis, and myocardial remodeling. Translational findings suggest that TREM2 expression correlates with cardiometabolic outcomes, underscoring its potential as a therapeutic target. Key knowledge gaps include TREM2's temporal dynamics during disease progression, sex-specific effects, and interactions with recruited or resident macrophage activation in obesity and T2DM. Integrating mechanistic and translational insights is critical to harness TREM2's immunoregulatory potential for improving CVD outcomes in metabolic disorders.