17β-Estradiol (E<sub>2</sub>) Upregulates the ERα/SIRT1/PGC-1α Signaling Pathway and Protects Mitochondrial Function to Prevent Bilateral Oophorectomy (OVX)-Induced Nonalcoholic Fatty Liver Disease (NAFLD)
Premature menopause is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD). Menopausal hormone therapy (MHT) has been widely used in clinical practice and has the potential to protect mitochondrial function and alleviate NAFLD. After bilateral oophorectomy (OVX), fema...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/12/2100 |
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| author | Ying Tian Xinyu Hong Yuan Xie Zaixin Guo Qi Yu |
| author_facet | Ying Tian Xinyu Hong Yuan Xie Zaixin Guo Qi Yu |
| author_sort | Ying Tian |
| collection | DOAJ |
| description | Premature menopause is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD). Menopausal hormone therapy (MHT) has been widely used in clinical practice and has the potential to protect mitochondrial function and alleviate NAFLD. After bilateral oophorectomy (OVX), female rats without 17β-estradiol (E<sub>2</sub>) intervention developed NAFLD, whereas E<sub>2</sub> supplementation was effective in preventing NAFLD in female rats. The altered pathways and cellular events from both comparison pairs, namely, the OVX vs. sham group and the OVX vs. E<sub>2</sub> group, were assessed using transcriptomic analysis. KEGG pathways enriched by both transcriptomic and metabolomic analyses strongly suggest that oxidative phosphorylation is a vital pathway that changes during the development of NAFLD and remains unchanged when E<sub>2</sub> is applied. Liver tissue from the OVX-induced NAFLD group exhibited increased lipid peroxidation, impaired mitochondria, and downregulated ERα/SIRT1/PGC-1α expression. An in vitro study indicated that the protective effect of E<sub>2</sub> treatment on hepatic steatosis could be abolished when ERα or SIRT1 was selectively inhibited. This damage was accompanied by reduced mitochondrial complex activity and increased lipid peroxidation. The current research indicates that E<sub>2</sub> upregulates the ERα/SIRT1/PGC-1α signaling pathway and protects mitochondrial function to prevent OVX-induced NAFLD. |
| first_indexed | 2024-03-08T21:02:58Z |
| format | Article |
| id | doaj.art-d343eb4d54794f4891faaae47fec716e |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-08T21:02:58Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-d343eb4d54794f4891faaae47fec716e2023-12-22T13:48:32ZengMDPI AGAntioxidants2076-39212023-12-011212210010.3390/antiox1212210017β-Estradiol (E<sub>2</sub>) Upregulates the ERα/SIRT1/PGC-1α Signaling Pathway and Protects Mitochondrial Function to Prevent Bilateral Oophorectomy (OVX)-Induced Nonalcoholic Fatty Liver Disease (NAFLD)Ying Tian0Xinyu Hong1Yuan Xie2Zaixin Guo3Qi Yu4Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus), No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730, ChinaDepartment of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus), No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730, ChinaDepartment of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus), No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730, ChinaDepartment of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus), No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730, ChinaDepartment of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus), No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730, ChinaPremature menopause is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD). Menopausal hormone therapy (MHT) has been widely used in clinical practice and has the potential to protect mitochondrial function and alleviate NAFLD. After bilateral oophorectomy (OVX), female rats without 17β-estradiol (E<sub>2</sub>) intervention developed NAFLD, whereas E<sub>2</sub> supplementation was effective in preventing NAFLD in female rats. The altered pathways and cellular events from both comparison pairs, namely, the OVX vs. sham group and the OVX vs. E<sub>2</sub> group, were assessed using transcriptomic analysis. KEGG pathways enriched by both transcriptomic and metabolomic analyses strongly suggest that oxidative phosphorylation is a vital pathway that changes during the development of NAFLD and remains unchanged when E<sub>2</sub> is applied. Liver tissue from the OVX-induced NAFLD group exhibited increased lipid peroxidation, impaired mitochondria, and downregulated ERα/SIRT1/PGC-1α expression. An in vitro study indicated that the protective effect of E<sub>2</sub> treatment on hepatic steatosis could be abolished when ERα or SIRT1 was selectively inhibited. This damage was accompanied by reduced mitochondrial complex activity and increased lipid peroxidation. The current research indicates that E<sub>2</sub> upregulates the ERα/SIRT1/PGC-1α signaling pathway and protects mitochondrial function to prevent OVX-induced NAFLD.https://www.mdpi.com/2076-3921/12/12/2100surgical menopausenonalcoholic fatty liver diseasemenopausal hormone therapymitochondriaoxidative stress |
| spellingShingle | Ying Tian Xinyu Hong Yuan Xie Zaixin Guo Qi Yu 17β-Estradiol (E<sub>2</sub>) Upregulates the ERα/SIRT1/PGC-1α Signaling Pathway and Protects Mitochondrial Function to Prevent Bilateral Oophorectomy (OVX)-Induced Nonalcoholic Fatty Liver Disease (NAFLD) Antioxidants surgical menopause nonalcoholic fatty liver disease menopausal hormone therapy mitochondria oxidative stress |
| title | 17β-Estradiol (E<sub>2</sub>) Upregulates the ERα/SIRT1/PGC-1α Signaling Pathway and Protects Mitochondrial Function to Prevent Bilateral Oophorectomy (OVX)-Induced Nonalcoholic Fatty Liver Disease (NAFLD) |
| title_full | 17β-Estradiol (E<sub>2</sub>) Upregulates the ERα/SIRT1/PGC-1α Signaling Pathway and Protects Mitochondrial Function to Prevent Bilateral Oophorectomy (OVX)-Induced Nonalcoholic Fatty Liver Disease (NAFLD) |
| title_fullStr | 17β-Estradiol (E<sub>2</sub>) Upregulates the ERα/SIRT1/PGC-1α Signaling Pathway and Protects Mitochondrial Function to Prevent Bilateral Oophorectomy (OVX)-Induced Nonalcoholic Fatty Liver Disease (NAFLD) |
| title_full_unstemmed | 17β-Estradiol (E<sub>2</sub>) Upregulates the ERα/SIRT1/PGC-1α Signaling Pathway and Protects Mitochondrial Function to Prevent Bilateral Oophorectomy (OVX)-Induced Nonalcoholic Fatty Liver Disease (NAFLD) |
| title_short | 17β-Estradiol (E<sub>2</sub>) Upregulates the ERα/SIRT1/PGC-1α Signaling Pathway and Protects Mitochondrial Function to Prevent Bilateral Oophorectomy (OVX)-Induced Nonalcoholic Fatty Liver Disease (NAFLD) |
| title_sort | 17β estradiol e sub 2 sub upregulates the erα sirt1 pgc 1α signaling pathway and protects mitochondrial function to prevent bilateral oophorectomy ovx induced nonalcoholic fatty liver disease nafld |
| topic | surgical menopause nonalcoholic fatty liver disease menopausal hormone therapy mitochondria oxidative stress |
| url | https://www.mdpi.com/2076-3921/12/12/2100 |
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