Adipose precursor cell-derived clusterin promotes homeostasis in subcutaneous adipose tissue

Adipose precursor cells (APCs), present within the stromal vascular fraction (SVF) of adipose tissue, play an important role in adipose biology. However, its regulatory functions in adipogenesis and tissue homeostasis remain incompletely characterized. Here, we isolated APC from the subcutaneous adipose tissue of Prx1-Cre; Rosa26-tdTomato mice and confirmed that APC has a high adipogenic differentiation efficiency. Next, RNA sequencing analysis indicates that APC may have dual effects of promoting adipogenesis and anti-inflammatory effects. Subsequent in vivo studies identified clusterin (Clu) as a key secretory factor through which APC exerts its regulatory functions. By utilizing gene regulation and APC/adipocyte co-culture, we further demonstrated that APC-derived Clu promotes its own adipogenic differentiation and improves local resistance to oxidative stress. Collectively, data from conditional Clu knockout mice establish its key function in preserving adipose tissue homeostasis. These findings highlight Clu as a potential therapeutic target for interventions aimed at adipose tissue homeostasis and regeneration.