Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice
Abstract Abnormal lipid metabolism and chronic low-grade inflammation are the main traits of obesity. Especially, the molecular mechanism of concomitant deficiency in steroidogenesis-associated enzymes related to testosterone (T) synthesis of obesity dominated a decline in male fertility is still po...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-11-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06162-8 |
| _version_ | 1797629943241244672 |
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| author | Jinyuan Wang Shun Zhang Linlin Hu Yan Wang Ke Liu Jianghua Le Yongpeng Tan Tianlong Li Haoxuan Xue Yanhong Wei Ou Zhong Junhui He Dan Zi Xin Lei Renhe Deng Yafei Luo Masong Tang Mingxuan Su Yichang Cao Qingyou Liu Zhihan Tang Xiaocan Lei |
| author_facet | Jinyuan Wang Shun Zhang Linlin Hu Yan Wang Ke Liu Jianghua Le Yongpeng Tan Tianlong Li Haoxuan Xue Yanhong Wei Ou Zhong Junhui He Dan Zi Xin Lei Renhe Deng Yafei Luo Masong Tang Mingxuan Su Yichang Cao Qingyou Liu Zhihan Tang Xiaocan Lei |
| author_sort | Jinyuan Wang |
| collection | DOAJ |
| description | Abstract Abnormal lipid metabolism and chronic low-grade inflammation are the main traits of obesity. Especially, the molecular mechanism of concomitant deficiency in steroidogenesis-associated enzymes related to testosterone (T) synthesis of obesity dominated a decline in male fertility is still poorly understood. Here, we found that in vivo, supplementation of pyrroloquinoline quinone (PQQ) efficaciously ameliorated the abnormal lipid metabolism and testicular spermatogenic function from high-fat-diet (HFD)-induced obese mice. Moreover, the transcriptome analysis of the liver and testicular showed that PQQ supplementation not only inhibited the high expression of proprotein convertase subtilisin/Kexin type 9 (PCSK9) but also weakened the NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis, which both played a negative role in T synthesis of Leydig Cells (LCs). Eventually, the function and the pyroptosis of LCs cultured with palmitic acid in vitro were simultaneously benefited by suppressing the expression of NLRP3 or PCSK9 respectively, as well the parallel effects of PQQ were affirmed. Collectively, our data revealed that PQQ supplementation is a feasible approach to protect T synthesis from PCSK9-NLRP3 crosstalk-induced LCs’ pyroptosis in obese men. |
| first_indexed | 2024-03-11T10:59:57Z |
| format | Article |
| id | doaj.art-31eee3c6713443e5b3b234a7b96ac03b |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-11T10:59:57Z |
| publishDate | 2023-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-31eee3c6713443e5b3b234a7b96ac03b2023-11-12T12:31:32ZengNature Publishing GroupCell Death and Disease2041-48892023-11-01141111910.1038/s41419-023-06162-8Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese miceJinyuan Wang0Shun Zhang1Linlin Hu2Yan Wang3Ke Liu4Jianghua Le5Yongpeng Tan6Tianlong Li7Haoxuan Xue8Yanhong Wei9Ou Zhong10Junhui He11Dan Zi12Xin Lei13Renhe Deng14Yafei Luo15Masong Tang16Mingxuan Su17Yichang Cao18Qingyou Liu19Zhihan Tang20Xiaocan Lei21Clinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaDepartment of Reproductive Medical Center, The Affiliated Hospital of Guilin Medical UniversityReproductive Medicine Center, The Affiliated Hospital of Youjiang Medical University for NationalitiesState Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi UniversityClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaDepartment of Reproductive Medical Center, The Affiliated Hospital of Guilin Medical UniversityClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaReproductive Medicine Center, The Affiliated Hospital of Youjiang Medical University for NationalitiesClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaState Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi UniversityClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Postdoctoral Station for Basic Medicine, Hengyang Medical School, University of South ChinaAbstract Abnormal lipid metabolism and chronic low-grade inflammation are the main traits of obesity. Especially, the molecular mechanism of concomitant deficiency in steroidogenesis-associated enzymes related to testosterone (T) synthesis of obesity dominated a decline in male fertility is still poorly understood. Here, we found that in vivo, supplementation of pyrroloquinoline quinone (PQQ) efficaciously ameliorated the abnormal lipid metabolism and testicular spermatogenic function from high-fat-diet (HFD)-induced obese mice. Moreover, the transcriptome analysis of the liver and testicular showed that PQQ supplementation not only inhibited the high expression of proprotein convertase subtilisin/Kexin type 9 (PCSK9) but also weakened the NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis, which both played a negative role in T synthesis of Leydig Cells (LCs). Eventually, the function and the pyroptosis of LCs cultured with palmitic acid in vitro were simultaneously benefited by suppressing the expression of NLRP3 or PCSK9 respectively, as well the parallel effects of PQQ were affirmed. Collectively, our data revealed that PQQ supplementation is a feasible approach to protect T synthesis from PCSK9-NLRP3 crosstalk-induced LCs’ pyroptosis in obese men.https://doi.org/10.1038/s41419-023-06162-8 |
| spellingShingle | Jinyuan Wang Shun Zhang Linlin Hu Yan Wang Ke Liu Jianghua Le Yongpeng Tan Tianlong Li Haoxuan Xue Yanhong Wei Ou Zhong Junhui He Dan Zi Xin Lei Renhe Deng Yafei Luo Masong Tang Mingxuan Su Yichang Cao Qingyou Liu Zhihan Tang Xiaocan Lei Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice Cell Death and Disease |
| title | Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice |
| title_full | Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice |
| title_fullStr | Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice |
| title_full_unstemmed | Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice |
| title_short | Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice |
| title_sort | pyrroloquinoline quinone inhibits pcsk9 nlrp3 mediated pyroptosis of leydig cells in obese mice |
| url | https://doi.org/10.1038/s41419-023-06162-8 |
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