The rising prevalence of metabolic diseases represents a global health challenge, among which metabolically unhealthy normal-weight individuals constitute a largely ignored subgroup. Fine particulate matter (PM2.5), which contains substantial nanoscale particulate matter, is a recognized extrinsic environmental trigger of metabolic disorders in both obese and nonobese situations, whereas the loss of plasticity in inguinal white adipose tissue (iWAT) is a critical intrinsic pathological feature of metabolic diseases. However, the long-term metabolic effects of maternal PM2.5 exposure on nonobese offspring, particularly in iWAT plasticity, and underlying cellular mechanisms remain poorly understood. Here, we revealed that maternal PM2.5 exposure induced insulin resistance in middle-aged male mouse offspring and identified iWAT as a susceptible adipose depot with impaired plasticity, which is characterized by adipocyte hypertrophy, inflammation, fibrosis, and metabolic dysfunction. Using single-cell RNA sequencing on iWAT from middle-aged male mouse offspring, we found that maternal PM2.5 exposure altered the fate decisions of adipose-derived stem cells from adipogenesis to fibrosis through increasing CD142+ adipogenesis-regulatory cell expansion and inducing fibrogenesis in DPP4+ adipose stem cells. Mechanistically, maternal PM2.5 exposure induced IgG production from plasma cells, which promoted fibrogenesis in DPP4+ adipose stem cells by activating macrophages. This process was further exacerbated by monocyte- and macrophage-mediated inflammation. Finally, maternal PM2.5 exposure induced endothelial cell heterogeneity shifts and dysfunction, facilitating immune cell recruitment and naïve B cell differentiation into plasma cells, ultimately initiating IgG-triggered plasticity impairment. This study provided insights into the adverse effects of maternal exposure to environmental pollution on the metabolic health of offspring at single-cell resolution.
Hu et al. (2026) studied this question.