PPARγ As a Potential Target for Adipogenesis Induced by Fine Particulate Matter in 3T3-L1 Preadipocytes
Yaqiang Cao, Yuanyuan Chen, Ke Miao, Shuyi Zhang, Fuchang Deng, Zhu Mu, Chao Wang, Wen Gu, Yixuan Huang, Zijin Shao, Xiaoyan Dong, Yufeng Gong, Hui Peng, Hui Yang, Yi Wan, Xudong Jia, Song Tang
Abstract
Mounting evidence has shown that ambient PM 2.5 exposure is closely associated with the development of obesity, and adipose tissue represents an important endocrine target for PM 2.5 . In this study, the 3T3-L1 preadipocyte differentiation model was employed to comprehensively explore the adipogenic potential of PM 2.5 . After 8 days of PM 2.5 exposure, adipocyte fatty acid uptake and lipid accumulation were significantly increased, and adipogenic differentiation of 3T3-L1 cells was promoted in a concentration-dependent manner. Transcriptome and lipidome analyses revealed the systematic disruption of transcriptional and lipid profiling at 10 μg/mL PM 2.5 . Functional enrichment and visualized network analyses showed that the peroxisome proliferator-activated receptor (PPAR) pathway and the metabolism of glycerophospholipids, glycerolipids, and sphingolipids were most significantly affected during adipocyte differentiation. Reporter gene assays indicated that PPARγ was activated by PM 2.5, demonstrating that PM 2.5 promoted adipogenesis by activating PPARγ. The increased transcriptional and protein expressions of PPARγ and downstream adipogenesis-associated markers ( e.g., Fabp4 and CD36) were further cross-validated using qRT-PCR and western blot. PM 2.5 -induced adipogenesis, PPARγ pathway activation, and lipid remodeling were significantly attenuated by the supplementation of a PPARγ antagonist (T0070907). Overall, this study yielded mechanistic insights into PM 2.5 -induced adipogenesis in vitro by identifying the potential biomolecular targets for the prevention of PM 2.5 -induced obesity and related metabolic diseases.