Purinergic 2X7 receptor is involved in adipogenesis and lipid degradation.
Purinergic 2X7 receptor is involved in adipogenesis and lipid degradation.
复制标题
嘌呤能2X7受体参与脂肪形成和脂质降解。
DOI：
10.3892/etm.2021.11004
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发表时间：
2022-01
影响因子：
2.7
通讯作者：
Xu Q
中科院分区：
文献类型：
--
作者：
Li J;Gong L;Xu Q
肥胖和血脂异常是严重影响患者健康的两种代谢综合征疾病。嘌呤能2X受体配基门控离子通道7(P2X7R)在调节脂质储存和代谢中起着重要作用。然而，P2X7R在脂肪形成和脂质降解中的作用和潜在机制仍不清楚。本研究通过喂饲高脂饲料建立小鼠肥胖模型，并利用3T3-L1细胞系体外分析了P2X7R的功能。逆转录-定量聚合酶链式反应和免疫印迹分析检测P2X7R、固醇调节元件结合蛋白1(SREBP1)等相关转录因子的表达水平。用生物信息学分析预测了P2X7R的潜在靶基因，并用双荧光素酶报告基因分析证实了这一预测。油红O染色评价前脂肪细胞的成脂能力。分别用脂肪红法、胆固醇法和游离甘油试剂检测甘油三酯(TGS)、总胆固醇(TC)和甘油的表达水平。结果表明，在肥胖小鼠中，P2X7R高表达，并参与了体外成脂分化过程。SREBP1增强了P2X7R的转录活性，促进其表达。抑制P2X7R显著降低前脂肪细胞的成脂能力，降低成脂相关转录因子(过氧化物酶体增殖物激活受体γ、CCAAT增强子结合蛋白α和脂肪酸结合蛋白4)的表达水平，增强脂解酶(脂肪甘油三酯脂肪酶、磷酸化激素敏感脂肪酶和单酰甘油脂肪酶)的表达水平，并调节成熟3T3-L1细胞的甘油三酯、总胆固醇和甘油的表达。这些效应被针对Wnt3a的小干扰RNA逆转。因此，本研究结果提示，转录活性受SREBP1调控的P2X7R通过靶向SREBP1调控脂肪生成和脂质降解，提示其对肥胖相关代谢具有潜在的作用。
Obesity and dyslipidemia are two metabolic syndrome disorders that have serious effects on the health of patients. Purinergic 2X receptor ligand-gated ion channel 7 (P2X7R) has been reported to play a role in regulating lipid storage and metabolism. However, the role and potential mechanism of P2X7R in adipogenesis and lipid degradation remain unknown. In the present study, a mouse model of obesity was established by feeding mice a high-fat diet, and the 3T3-L1 cell line was used to analyze the function of P2X7R in vitro. Reverse transcription-quantitative PCR and western blot analyses were performed to detect the expression levels of P2X7R, sterol regulatory element-binding protein 1 (SREBP1) and other associated transcription factors. Bioinformatics analysis was used to predict the potential target gene of P2X7R and a dual luciferase reporter assay was used to confirm this prediction. Oil Red O staining was used to evaluate the adipogenic capacity of preadipocytes. AdipoRed assay, cholesterol assay and a free glycerol reagent were used to measure the expression levels of triglyceride (TGs), total cholesterol (TC) and glycerin, respectively. The results indicated that P2X7R was highly expressed in obese mice and that it was involved in adipogenic differentiation in vitro. SREBP1 enhanced the transcription activities of P2X7R to promote its expression. Inhibition of P2X7R significantly reduced the adipogenic capacity of preadipocytes, decreased the expression levels of adipogenesis-associated transcription factors (peroxisome proliferator-activated receptor γ, CCAAT-enhancer-binding protein α and fatty-acid-binding protein 4), enhanced the expression levels of lipolytic enzymes (adipose triglyceride lipase, phosphorylated hormone-sensitive lipase and monoacylglycerol lipase) and regulated the expression of TG, TC and glycerin in mature 3T3-L1 cells. These effects were reversed by a small interfering RNA targeting Wnt3a. Therefore, the results suggested that P2X7R, the transcription activities of which were regulated by SREBP1, regulated adipogenesis and lipid degradation by targeting SREBP1, indicating its potential effects on obesity-associated metabolism.
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影响因子：
6.1
作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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