Inhibition of Col6a5 Improve Lipid Metabolism Disorder in Dihydrotestosterone-Induced Hyperandrogenic Mice
Hyperandrogenism is a key pathological feature of polycystic ovarian syndrome (PCOS). Excess androgen can lead to PCOS-like cell hypertrophy in the ovaries and adipose tissue of rodents. Here, we established a dihydrotestosterone (DHT)-induced hyperandrogenic mouse model to analyze the differences i...
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.669189/full |
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| author | Li-Feng Sun Ya-Li Yang Ya-Li Yang Mei-Yue Wang Mei-Yue Wang Hua-Shan Zhao Hua-Shan Zhao Tian-xia Xiao Meng-Xia Li Bao-Bei Wang Chen Huang Chen Huang Pei-Gen Ren Pei-Gen Ren Jian V. Zhang Jian V. Zhang |
| author_facet | Li-Feng Sun Ya-Li Yang Ya-Li Yang Mei-Yue Wang Mei-Yue Wang Hua-Shan Zhao Hua-Shan Zhao Tian-xia Xiao Meng-Xia Li Bao-Bei Wang Chen Huang Chen Huang Pei-Gen Ren Pei-Gen Ren Jian V. Zhang Jian V. Zhang |
| author_sort | Li-Feng Sun |
| collection | DOAJ |
| description | Hyperandrogenism is a key pathological feature of polycystic ovarian syndrome (PCOS). Excess androgen can lead to PCOS-like cell hypertrophy in the ovaries and adipose tissue of rodents. Here, we established a dihydrotestosterone (DHT)-induced hyperandrogenic mouse model to analyze the differences in gene expression and signaling pathways of the ovaries and gonad fat pads of mice treated with or without DHT by RNA microarray analysis. From the results, we focused on the overlapping differentially expressed gene—Col6a5—and the major differentially enriched signaling pathway—lipid metabolism. We employed DHT-induced mouse ovarian stromal cell, adipogenic 3T3-L1 cell and hepatic cell line NCTC1469 models to investigate whether androgens directly mediate lipid accumulation and hypertrophy. We found that DHT increased lipid droplet accumulation in ovarian stromal cells and adipogenic 3T3-L1 cells but not NCTC1469 cells. DHT significantly altered stromal cell cholesterol metabolism and steroidogenesis, as indicated by changes in cholesterol levels and the expression of related genes, but these effects were not observed in 3T3-L1 cells. Moreover, Col6a5 expression was significantly increased in ovaries and gonadal fat pads of DHT-treated mice, and Col6a5 inhibition alleviated DHT-induced excess lipid accumulation and hypertrophy of ovarian stromal cells and adipogenic 3T3-L1 cells, even improved lipid metabolism in overnourished NCTC1469 cells. Our results indicate that Col6a5 plays important roles in the pathogenesis of DHT-induced lipid metabolism disorder and the hypertrophy of ovarian stromal cells and adipocytes. |
| first_indexed | 2024-12-21T22:20:53Z |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T22:20:53Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-71cf0c2d71944877966e09b811e2edd12022-12-21T18:48:21ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-05-01910.3389/fcell.2021.669189669189Inhibition of Col6a5 Improve Lipid Metabolism Disorder in Dihydrotestosterone-Induced Hyperandrogenic MiceLi-Feng Sun0Ya-Li Yang1Ya-Li Yang2Mei-Yue Wang3Mei-Yue Wang4Hua-Shan Zhao5Hua-Shan Zhao6Tian-xia Xiao7Meng-Xia Li8Bao-Bei Wang9Chen Huang10Chen Huang11Pei-Gen Ren12Pei-Gen Ren13Jian V. Zhang14Jian V. Zhang15Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaCenter for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaShenzhen College of Advanced Technology, University of Chinese Academy of Sciences, Shenzhen, ChinaCenter for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaDepartment of Clinical Pharmacy and Translational Medicine, School of Pharmacy and Biomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaCenter for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaDepartment of Clinical Pharmacy and Translational Medicine, School of Pharmacy and Biomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaCenter for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaCenter for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaCenter for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaCenter for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaDepartment of Clinical Pharmacy and Translational Medicine, School of Pharmacy and Biomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaCenter for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaDepartment of Clinical Pharmacy and Translational Medicine, School of Pharmacy and Biomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaCenter for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaDepartment of Clinical Pharmacy and Translational Medicine, School of Pharmacy and Biomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaHyperandrogenism is a key pathological feature of polycystic ovarian syndrome (PCOS). Excess androgen can lead to PCOS-like cell hypertrophy in the ovaries and adipose tissue of rodents. Here, we established a dihydrotestosterone (DHT)-induced hyperandrogenic mouse model to analyze the differences in gene expression and signaling pathways of the ovaries and gonad fat pads of mice treated with or without DHT by RNA microarray analysis. From the results, we focused on the overlapping differentially expressed gene—Col6a5—and the major differentially enriched signaling pathway—lipid metabolism. We employed DHT-induced mouse ovarian stromal cell, adipogenic 3T3-L1 cell and hepatic cell line NCTC1469 models to investigate whether androgens directly mediate lipid accumulation and hypertrophy. We found that DHT increased lipid droplet accumulation in ovarian stromal cells and adipogenic 3T3-L1 cells but not NCTC1469 cells. DHT significantly altered stromal cell cholesterol metabolism and steroidogenesis, as indicated by changes in cholesterol levels and the expression of related genes, but these effects were not observed in 3T3-L1 cells. Moreover, Col6a5 expression was significantly increased in ovaries and gonadal fat pads of DHT-treated mice, and Col6a5 inhibition alleviated DHT-induced excess lipid accumulation and hypertrophy of ovarian stromal cells and adipogenic 3T3-L1 cells, even improved lipid metabolism in overnourished NCTC1469 cells. Our results indicate that Col6a5 plays important roles in the pathogenesis of DHT-induced lipid metabolism disorder and the hypertrophy of ovarian stromal cells and adipocytes.https://www.frontiersin.org/articles/10.3389/fcell.2021.669189/fulldihydrotestosteroneovarygonad fatCol6a5hypertrophylipid metabolism |
| spellingShingle | Li-Feng Sun Ya-Li Yang Ya-Li Yang Mei-Yue Wang Mei-Yue Wang Hua-Shan Zhao Hua-Shan Zhao Tian-xia Xiao Meng-Xia Li Bao-Bei Wang Chen Huang Chen Huang Pei-Gen Ren Pei-Gen Ren Jian V. Zhang Jian V. Zhang Inhibition of Col6a5 Improve Lipid Metabolism Disorder in Dihydrotestosterone-Induced Hyperandrogenic Mice Frontiers in Cell and Developmental Biology dihydrotestosterone ovary gonad fat Col6a5 hypertrophy lipid metabolism |
| title | Inhibition of Col6a5 Improve Lipid Metabolism Disorder in Dihydrotestosterone-Induced Hyperandrogenic Mice |
| title_full | Inhibition of Col6a5 Improve Lipid Metabolism Disorder in Dihydrotestosterone-Induced Hyperandrogenic Mice |
| title_fullStr | Inhibition of Col6a5 Improve Lipid Metabolism Disorder in Dihydrotestosterone-Induced Hyperandrogenic Mice |
| title_full_unstemmed | Inhibition of Col6a5 Improve Lipid Metabolism Disorder in Dihydrotestosterone-Induced Hyperandrogenic Mice |
| title_short | Inhibition of Col6a5 Improve Lipid Metabolism Disorder in Dihydrotestosterone-Induced Hyperandrogenic Mice |
| title_sort | inhibition of col6a5 improve lipid metabolism disorder in dihydrotestosterone induced hyperandrogenic mice |
| topic | dihydrotestosterone ovary gonad fat Col6a5 hypertrophy lipid metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.669189/full |
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