Inhibition of mmu_circ_0009303 improves metabolic dysfunction-associated steatotic liver disease by regulating lipid metabolism and oxidative stress
Circular RNAs (circRNAs) play an important role in regulating inflammation and oxidative stress during the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanism is unclear. This study aimed to determine the role of mmu_circ_0009303 in MAS...
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The Japan Endocrine Society
2025-01-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/72/1/72_EJ24-0008/_html/-char/en |
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| author | Ju Zhou Wu Li Xiaowei Chi Dingchun Li Chunxia Yang Zhiwen Duan |
| author_facet | Ju Zhou Wu Li Xiaowei Chi Dingchun Li Chunxia Yang Zhiwen Duan |
| author_sort | Ju Zhou |
| collection | DOAJ |
| description | Circular RNAs (circRNAs) play an important role in regulating inflammation and oxidative stress during the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanism is unclear. This study aimed to determine the role of mmu_circ_0009303 in MASLD. We used a bioinformatics approach to identify potential targets and established an in vitro model of MASLD. Oil red O staining, cell transfection and dual-luciferase reporter assay were used to determine the role of mmu_circ_0009303. The results indicated that the mmu_circ_0009303 expression was significantly increased in the MASLD model both in vitro and in vivo and was associated with oxidative stress levels and inflammation. Moreover, bioinformatics analyses revealed that miRNA-182-5p and Foxo3 are targets of mmu_circ_0009303 and miRNA-182-5p, respectively. In the in vitro MASLD model, mmu_circ_0009303 promoted fat deposition in NCTC1469 cells, which was induced by free fatty acid (FFA) through the regulation of miRNA-182-5p/Foxo3. The expression of miRNA-182-5p and Forkhead box O3 (Foxo3) was associated with mmu_circ_0009303 expression in the liver of mice with MASLD, which was induced by a high-fat diet. Furthermore, mmu_circ_0009303 may be involved in regulating the expression of lipid metabolism-related regulatory proteins, such as CPT1A, SLC27A4, ACBD3, SREBP1, FAS, PPARα, and PPARγ. Taken together, mmu_circ_0009303 promotes oxidative stress, inflammation, and excessive fat accumulation in NCTC1469 cells induced by FFA through the regulation of miRNA-182-5p/Foxo3 and lipid metabolism-related regulatory proteins. These findings provide a potential target for the treatment of MASLD. |
| format | Article |
| id | doaj-art-0bd18f957167481fbb0431e680d4f84c |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-0bd18f957167481fbb0431e680d4f84c2025-01-22T05:36:47ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402025-01-01721799110.1507/endocrj.EJ24-0008endocrjInhibition of mmu_circ_0009303 improves metabolic dysfunction-associated steatotic liver disease by regulating lipid metabolism and oxidative stressJu Zhou0Wu Li1Xiaowei Chi2Dingchun Li3Chunxia Yang4Zhiwen Duan5Department of Infectious Disease, The First Affiliated Hospital, Kunming Medical University, Kunming 650032, ChinaDepartment of Infectious Disease, The First Affiliated Hospital, Kunming Medical University, Kunming 650032, ChinaDepartment of Infectious Disease, The First Affiliated Hospital, Kunming Medical University, Kunming 650032, ChinaDepartment of Infectious Disease, The First Affiliated Hospital, Kunming Medical University, Kunming 650032, ChinaDepartment of Infectious Disease, The First Affiliated Hospital, Kunming Medical University, Kunming 650032, ChinaDepartment of Infectious Disease, The First Affiliated Hospital, Kunming Medical University, Kunming 650032, ChinaCircular RNAs (circRNAs) play an important role in regulating inflammation and oxidative stress during the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanism is unclear. This study aimed to determine the role of mmu_circ_0009303 in MASLD. We used a bioinformatics approach to identify potential targets and established an in vitro model of MASLD. Oil red O staining, cell transfection and dual-luciferase reporter assay were used to determine the role of mmu_circ_0009303. The results indicated that the mmu_circ_0009303 expression was significantly increased in the MASLD model both in vitro and in vivo and was associated with oxidative stress levels and inflammation. Moreover, bioinformatics analyses revealed that miRNA-182-5p and Foxo3 are targets of mmu_circ_0009303 and miRNA-182-5p, respectively. In the in vitro MASLD model, mmu_circ_0009303 promoted fat deposition in NCTC1469 cells, which was induced by free fatty acid (FFA) through the regulation of miRNA-182-5p/Foxo3. The expression of miRNA-182-5p and Forkhead box O3 (Foxo3) was associated with mmu_circ_0009303 expression in the liver of mice with MASLD, which was induced by a high-fat diet. Furthermore, mmu_circ_0009303 may be involved in regulating the expression of lipid metabolism-related regulatory proteins, such as CPT1A, SLC27A4, ACBD3, SREBP1, FAS, PPARα, and PPARγ. Taken together, mmu_circ_0009303 promotes oxidative stress, inflammation, and excessive fat accumulation in NCTC1469 cells induced by FFA through the regulation of miRNA-182-5p/Foxo3 and lipid metabolism-related regulatory proteins. These findings provide a potential target for the treatment of MASLD.https://www.jstage.jst.go.jp/article/endocrj/72/1/72_EJ24-0008/_html/-char/enmetabolic dysfunction-associated steatotic liver disease (masld)mmu_circ_0009303mirna-182-5pforkhead box o3 (foxo3) |
| spellingShingle | Ju Zhou Wu Li Xiaowei Chi Dingchun Li Chunxia Yang Zhiwen Duan Inhibition of mmu_circ_0009303 improves metabolic dysfunction-associated steatotic liver disease by regulating lipid metabolism and oxidative stress Endocrine Journal metabolic dysfunction-associated steatotic liver disease (masld) mmu_circ_0009303 mirna-182-5p forkhead box o3 (foxo3) |
| title | Inhibition of mmu_circ_0009303 improves metabolic dysfunction-associated steatotic liver disease by regulating lipid metabolism and oxidative stress |
| title_full | Inhibition of mmu_circ_0009303 improves metabolic dysfunction-associated steatotic liver disease by regulating lipid metabolism and oxidative stress |
| title_fullStr | Inhibition of mmu_circ_0009303 improves metabolic dysfunction-associated steatotic liver disease by regulating lipid metabolism and oxidative stress |
| title_full_unstemmed | Inhibition of mmu_circ_0009303 improves metabolic dysfunction-associated steatotic liver disease by regulating lipid metabolism and oxidative stress |
| title_short | Inhibition of mmu_circ_0009303 improves metabolic dysfunction-associated steatotic liver disease by regulating lipid metabolism and oxidative stress |
| title_sort | inhibition of mmu circ 0009303 improves metabolic dysfunction associated steatotic liver disease by regulating lipid metabolism and oxidative stress |
| topic | metabolic dysfunction-associated steatotic liver disease (masld) mmu_circ_0009303 mirna-182-5p forkhead box o3 (foxo3) |
| url | https://www.jstage.jst.go.jp/article/endocrj/72/1/72_EJ24-0008/_html/-char/en |
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