吡咯列酮调控脂肪细胞分化的药理学研究

doi:10.5246/jcps.2022.03.015

中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (3): 176-183.DOI: 10.5246/jcps.2022.03.015

吡咯列酮调控脂肪细胞分化的药理学研究

秦川, 万琪, 席蕾, 魏冕, 杜权^*()

北京大学医学部药学院天然药物及仿生药物国家重点实验室, 北京 100191

收稿日期:2021-10-11 修回日期:2021-11-05 接受日期:2021-12-08 出版日期:2022-03-31 发布日期:2022-03-31
通讯作者: 杜权
作者简介:
+ Tel.: +86-10-82805780, E-mail: quan.du@pku.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 3207040249).

A pharmacological study of pioglitazone in the regulation of adipocyte differentiation

Chuan Qin, Qi Wan, Lei Xi, Mian Wei, Quan Du^*()

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2021-10-11 Revised:2021-11-05 Accepted:2021-12-08 Online:2022-03-31 Published:2022-03-31
Contact: Quan Du

摘要/Abstract

摘要：

作为脂肪细胞分化异常的一个病理性结果, 肥胖不仅会导致体重增加、能量代谢异常, 还会进一步引起糖尿病等重大疾病的发生。该领域早期的研究侧重于蛋白调控因子的发现和功能研究, 近年来的工作表明长非编码RNA也积极地参与了脂肪细胞分化过程的调控。通过文献调研, 我们了解到在糖尿病的治疗过程中, 长期服用吡咯列酮会使患者体重增加, 导致肥胖, 但相关的机制研究还未见报道。本研究中, 我们利用3T3-L1脂肪细胞体外诱导分化模型, 系统地分析了吡咯列酮对分化过程的影响。利用油红O和Bodioy荧光染色, 发现吡咯列酮处理能促进脂肪细胞的分化。随后, 我们分析了药物处理对PPARγ、C/EBPα、FABP4以及CD36表达的影响, 从蛋白信号通路的角度对这一过程进行了研究。此外, 我们还分析了吡咯列酮处理对课题组前期鉴定的一条促脂肪细胞分化的长非编码RNA slincRAD表达的影响。

关键词: 长非编码RNA, 脂肪细胞分化, 吡咯列酮, slincRAD

Abstract:

As a pathological result of the abnormal differentiation of adipocytes, the occurrence of obesity will not only lead to weight gain, abnormal energy metabolism, but also the development of the diseases such as diabetes. Early studies have focused on the discovery of protein factors that regulate this process. Recently, long noncoding RNAs (lncRNAs) are found to actively participate in the process of adipocyte differentiation. By means of literature investigation, we get to know that in the treatment of diabetes, taking pioglitazone for a long time will lead to weight gain and obesity. However, the undeerlying mechanisms are far from being clarified. To this aspect, the effects of pioglitazone treatment on adipocyte differentiation were systematically investigated, in the present study. Using an in vitro adipocyte differentiation model of 3T3-L1 cells, pioglitazone treatment was found to promot the process of differentiation. Studies were then performed with the effects on protein signaling pathway, in terms of the expressional regulation of PPARγ, C/EBPα, FABP4 and CD36. To further elucidate the effects of pioglitazone, regulation of a adipogenic lncRNA was also investigated in the study.

Key words: Long non-coding RNA, Adipocyte differentiation, Pioglitazone, slincRAD

Supporting:

秦川, 万琪, 席蕾, 魏冕, 杜权. 吡咯列酮调控脂肪细胞分化的药理学研究[J]. 中国药学(英文版), 2022, 31(3): 176-183.

Chuan Qin, Qi Wan, Lei Xi, Mian Wei, Quan Du. A pharmacological study of pioglitazone in the regulation of adipocyte differentiation[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(3): 176-183.

图/表 6

Figure 1. The effects of pioglitazone treatment on adipocyte differentiation of 3T3-L1 cells. (a) Results of Oil red O staining on day 6 of differentiation. Scale bars, 100 μM; (b) The absorbance of Oil red O staining. Data are presented as mean ± SD (student’s t-test, n = 6); ***, P < 0.001. PIO, pioglitazone-treated group; DMSO, pioglitazone-untreated control group. OD, absorbance.

Figure 2. The effects of pioglitazone treatment on day 12 of differentiation. (a) The results of Oil red O staining on day 12. Scale bar, 100 μM; (b) The absorbance of Oil red O staining. Data are presented as mean ± SD (student’s t-test, n = 6). PIO, pioglitazone-treated group; DMSO, pioglitazone-untreated control group. OD, absorbance.

Figure 3. The effects of pioglitazone treatment made by BODIPY staining. (a) Results of BODIPY staining on day 6 of differentiation. Scale bar, 20 μM; (b) Semi-quantitative analyses of BODIPY staining.

Figure 4. The effect of pioglitazone on 3T3-L1 cell activity. The cell proliferation activity was determined by CCK-8 staining, n = 6.

Figure 5. The effects of pioglitazone treatment on gene expression of key transcription factors. (a) The effects on PPAR?? expression. (b) The effects on C/EBP?? expression. (c) The effects on FABP4 expression. (d) The effects on CD36 expression. Data are presented as mean ± SD (n = 3).

Figure 6. Effects of pioglitazone on the expression of slincRAD.

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吡咯列酮调控脂肪细胞分化的药理学研究

A pharmacological study of pioglitazone in the regulation of adipocyte differentiation

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