PPARγ 作为 3T3-L1 前脂肪细胞细颗粒物诱导脂肪生成的潜在靶点,Environmental Science & Technology

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PPARγ 作为 3T3-L1 前脂肪细胞细颗粒物诱导脂肪生成的潜在靶点
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2023-05-11 , DOI: 10.1021/acs.est.2c09361
Yaqiang Cao _{1,

2,

3} , Yuanyuan Chen _{1,

4} , Ke Miao ₁ , Shuyi Zhang _{1,

3} , Fuchang Deng ₁ , Mu Zhu ₁ , Chao Wang ₁ , Wen Gu _{1,

4} , Yixuan Huang ₅ , Zijin Shao _{1,

6} , Xiaoyan Dong ₁ , Yufeng Gong ₇ , Hui Peng ₇ , Hui Yang ₈ , Yi Wan ₅ , Xudong Jia ₈ , Song Tang _{1,

3}

Affiliation

越来越多的证据表明，环境 PM _2.5暴露与肥胖的发展密切相关，脂肪组织是 PM _2.5的重要内分泌目标。本研究采用3T3-L1前脂肪细胞分化模型，全面探索PM _2.5的成脂潜力。暴露于PM _2.5 8天后，脂肪细胞脂肪酸摄取和脂质积累显着增加，并以浓度依赖性方式促进3T3-L1细胞的成脂分化。_{转录组和脂质组分析揭示了在 10 μg/mL PM 2.5}时转录和脂质谱的系统性破坏. 功能富集和可视化网络分析表明，过氧化物酶体增殖物激活受体 (PPAR) 通路和甘油磷脂、甘油脂和鞘脂的代谢在脂肪细胞分化过程中受到的影响最为显着。报告基因分析表明 PPARγ 被 PM _2.5激活，证明 PM _2.5通过激活 PPARγ 促进脂肪形成。使用 qRT-PCR 和蛋白质印迹进一步交叉验证PPARγ 和下游脂肪生成相关标记物（例如Fabp4 和 CD36）的转录和蛋白质表达增加。颗粒物_2.5诱导的脂肪形成、PPARγ 通路激活和脂质重塑通过补充 PPARγ 拮抗剂 (T0070907) 显着减弱。总的来说，这项研究通过确定用于预防PM _2.5诱导的肥胖和相关代谢疾病的潜在生物分子靶点，对 PM _{2.5诱导的体外}脂肪生成机制有了深入的了解。

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PPARγ As a Potential Target for Adipogenesis Induced by Fine Particulate Matter in 3T3-L1 Preadipocytes

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.

更新日期：2023-05-11

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