Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling
Abstract Knowledge gaps that limit the development of therapies for polycystic ovary syndrome (PCOS) concern various environmental factors that impact clinical characteristics. Circadian dysrhythmia contributes to glycometabolic and reproductive hallmarks of PCOS. Here, we illustrated the ameliorati...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-023-00415-2 |
| _version_ | 1797784749140344832 |
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| author | Shang Li Junyu Zhai Weiwei Chu Xueying Geng Dongshuang Wang Luwei Jiao Gang Lu Wai-Yee Chan Kang Sun Yun Sun Zi-Jiang Chen Yanzhi Du |
| author_facet | Shang Li Junyu Zhai Weiwei Chu Xueying Geng Dongshuang Wang Luwei Jiao Gang Lu Wai-Yee Chan Kang Sun Yun Sun Zi-Jiang Chen Yanzhi Du |
| author_sort | Shang Li |
| collection | DOAJ |
| description | Abstract Knowledge gaps that limit the development of therapies for polycystic ovary syndrome (PCOS) concern various environmental factors that impact clinical characteristics. Circadian dysrhythmia contributes to glycometabolic and reproductive hallmarks of PCOS. Here, we illustrated the amelioration of Limosilactobacillus reuteri (L. reuteri) on biorhythm disorder-ignited dyslipidemia of PCOS via a microbiota-metabolite-liver axis. A rat model of long-term (8 weeks) darkness treatment was used to mimic circadian dysrhythmia-induced PCOS. Hepatic transcriptomics certified by in vitro experiments demonstrated that increased hepatic galanin receptor 1 (GALR1) due to darkness exposure functioned as a critical upstream factor in the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway to suppress nuclear receptors subfamily 1, group D, member 1 (NR1D1) and promoted sterol regulatory element binding protein 1 (SREBP1), inducing lipid accumulation in the liver. Further investigations figured out a restructured microbiome-metabolome network following L. reuteri administration to protect darkness rats against dyslipidemia. Notably, L. reuteri intervention resulted in the decrease of Clostridium sensu stricto 1 and Ruminococcaceae UCG-010 as well as gut microbiota-derived metabolite capric acid, which could further inhibit GALR1-NR1D1-SREBP1 pathway in the liver. In addition, GALR antagonist M40 reproduced similar ameliorative effects as L. reuteri to protect against dyslipidemia. While exogenous treatment of capric acid restrained the protective effects of L. reuteri in circadian disruption-induced PCOS through inhibiting GALR1-dependent hepatic lipid metabolism. These findings purport that L. reuteri could serve for circadian disruption-associated dyslipidemia. Manipulation of L. reuteri–capric acid–GALR1 axis paves way for clinical therapeutic strategies to prevent biorhythm disorder-ignited dyslipidemia in PCOS women. |
| first_indexed | 2024-03-13T00:44:19Z |
| format | Article |
| id | doaj.art-3a0ec04d0532463ab4a68fe065b41ac4 |
| institution | Directory Open Access Journal |
| issn | 2055-5008 |
| language | English |
| last_indexed | 2024-03-13T00:44:19Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj.art-3a0ec04d0532463ab4a68fe065b41ac42023-07-09T11:08:01ZengNature Portfolionpj Biofilms and Microbiomes2055-50082023-07-019111810.1038/s41522-023-00415-2Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signalingShang Li0Junyu Zhai1Weiwei Chu2Xueying Geng3Dongshuang Wang4Luwei Jiao5Gang Lu6Wai-Yee Chan7Kang Sun8Yun Sun9Zi-Jiang Chen10Yanzhi Du11Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityCenter for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityCenter for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityCenter for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityCenter for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityCenter for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityThe Chinese University of Hong Kong-Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong KongThe Chinese University of Hong Kong-Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong KongCenter for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityCenter for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityCenter for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityCenter for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Knowledge gaps that limit the development of therapies for polycystic ovary syndrome (PCOS) concern various environmental factors that impact clinical characteristics. Circadian dysrhythmia contributes to glycometabolic and reproductive hallmarks of PCOS. Here, we illustrated the amelioration of Limosilactobacillus reuteri (L. reuteri) on biorhythm disorder-ignited dyslipidemia of PCOS via a microbiota-metabolite-liver axis. A rat model of long-term (8 weeks) darkness treatment was used to mimic circadian dysrhythmia-induced PCOS. Hepatic transcriptomics certified by in vitro experiments demonstrated that increased hepatic galanin receptor 1 (GALR1) due to darkness exposure functioned as a critical upstream factor in the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway to suppress nuclear receptors subfamily 1, group D, member 1 (NR1D1) and promoted sterol regulatory element binding protein 1 (SREBP1), inducing lipid accumulation in the liver. Further investigations figured out a restructured microbiome-metabolome network following L. reuteri administration to protect darkness rats against dyslipidemia. Notably, L. reuteri intervention resulted in the decrease of Clostridium sensu stricto 1 and Ruminococcaceae UCG-010 as well as gut microbiota-derived metabolite capric acid, which could further inhibit GALR1-NR1D1-SREBP1 pathway in the liver. In addition, GALR antagonist M40 reproduced similar ameliorative effects as L. reuteri to protect against dyslipidemia. While exogenous treatment of capric acid restrained the protective effects of L. reuteri in circadian disruption-induced PCOS through inhibiting GALR1-dependent hepatic lipid metabolism. These findings purport that L. reuteri could serve for circadian disruption-associated dyslipidemia. Manipulation of L. reuteri–capric acid–GALR1 axis paves way for clinical therapeutic strategies to prevent biorhythm disorder-ignited dyslipidemia in PCOS women.https://doi.org/10.1038/s41522-023-00415-2 |
| spellingShingle | Shang Li Junyu Zhai Weiwei Chu Xueying Geng Dongshuang Wang Luwei Jiao Gang Lu Wai-Yee Chan Kang Sun Yun Sun Zi-Jiang Chen Yanzhi Du Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling npj Biofilms and Microbiomes |
| title | Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling |
| title_full | Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling |
| title_fullStr | Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling |
| title_full_unstemmed | Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling |
| title_short | Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling |
| title_sort | alleviation of limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia induced dyslipidemia via capric acid and galr1 signaling |
| url | https://doi.org/10.1038/s41522-023-00415-2 |
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