White adipose tissue (WAT) expands through adipocyte hypertrophy or hyperplasia-associated differentiation of progenitor adipose stem cells (ASC). The triggering receptor expressed on myeloid cells 2 (TREM2) reportedly promotes adipocyte differentiation and whole body TREM2 deletion in mice leads to adipose hypertrophy and worsened metabolic health. However, whether TREM2 expression in ASC is involved is unknown. Here, we find TREM2 is expressed on platelet derived growth factor receptor-α (PDGFR-α) positive ASC in obesity. While global deletion of TREM2 strongly attenuated adipocyte differentiation in three different cell culture models, conditional TREM2 deletion within PDGFR-α + ASC impacted early adipocyte differentiation. Obese animals where TREM2 was specifically deleted in PDGFR-α + expressing cells exhibited moderately increased ASC, but WAT morphology, macrophage amounts as well as glucose and insulin tolerance were comparable to littermate controls. Thus, although TREM2 is important for adipocyte differentiation in cell culture, its expression in ASC is dispensable for WAT remodeling and metabolic health during obesity.
Dobrijević et al. (2026) studied this question.