Poplar type propolis influences the remodeling of the extracellular matrix in 3T3-L1 cells to reduce its differentiation and fat accumulation by inhibiting Col1a1

Obesity has become a significant public health issue worldwide, which is defined as the abnormal enlargement of adipose tissue. Inhibiting fat cell growth and accumulation has been a key strategy in anti-obesity treatments. Poplar type propolis has shown great anti-obesity effects, but its effect and mechanism of poplar type propolis on adipocyte differentiation and fat accumulation are still not fully understood. In this study, the main compounds in poplar type propolis extract (PPE) were identified and used to construct a pharmacological network, revealing that PPE has potential roles in cellular development, differentiation, and lipid synthesis. Furthermore, lipidomics analysis indicated that PPE could reduce the ability of 3T3-L1 cells to mature and differentiate into adipocytes, which was evidenced by decreased formation of large lipid droplets and reduced cell membrane fluidity, along with a significant decrease in glucose uptake (67.45%) and fat accumulation (83.60%). Moreover, transcriptomics revealed PPE suppressed glycolysis in cells by steroid biosynthesis and PPAR signaling pathway by affected extracellular matrix remodeling during cell differentiation with Col1a1 was identified as an essential target of PPE affecting these processes through protein-protein interaction network and molecular docking. Finally, western blotting and immunofluorescence analysis were performed to validate the regulatory effect of PPE on Col1a1 expression. In conclusion, this study reveals a novel anti-adipogenic mechanism of PPE by inhibiting Col1a1-dependent extracellular matrix remodeling, thereby suppressing 3T3-L1 adipocyte differentiation and lipid accumulation. This study provides robust experimental evidence and theoretical foundations for developing PPE as a functional food.