2082-LB: Heterogeneity in Adipose Progenitor (AP) Populations from Subcutaneous Abdominal and Thigh Adipose Tissues of Women

Introduction & Objective: Lower body fat distribution decreases risk for T2D, but the mechanisms involved are poorly understood. The objective of this study was to compare AP populations of paired samples of upper body abdominal (A) vs lower body thigh (T) adipose tissues that may contribute to this association.

Methods: Single nuclei RNA sequencing (snRNASeq) identified AP subclusters (Seurat); bioinformatic and within subject statistical comparisons used pseudobulk analyses and paired ttest. Cell-Cell communication analysis (CellChat) addressed depot-dependent mechanisms tissue homeostasis.

Results: Healthy, premenopausal women in this study were n=7, BMI (28.7+/- 6.3 kg/m²), age 30 +/-5.5 y, waist to hip ratio 0.79 +/- 0.02 (mean ± SD). APs (6489 (A), 7194 (T)) in 9 subclusters varied in their degree of adipogenic commitment. An early AP population expressed higher levels of CD55 in A than T, and low MGP and AREG/F3. Two other ‘early’ AP clusters expressed the highest levels of anti-adipogenic factors, AREG/F3 AP were more abundant in T (9% vs 6%, p<0.007; 5.4 vs 3.7%, p=0.025). A small population (5%) of committed ‘preadipocytes’ was in both depots. Additional clusters had high expression of secreted adipokines and extracellular matrix factors and secretory pathways (Collagens, Lumicans). We found evidence for higher cell-cell communication in T (FGF-FGFR, IGF-IGFR1, PDGF-PDGFR).

Conclusion: Our results suggest that higher expression of anti-adipogenic factors in TSAT maintain a larger pool of APs that can respond to pro-adipogenic signals, as needed, to better preserve tissue and systemic metabolic homeostasis in response to a stress (e.g. obesity).