Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity
Abstract Aging is a major risk factor for metabolic disorders. Polyunsaturated fatty acid-derived bioactive lipids play critical roles as signaling molecules in metabolic processes. Nonetheless, their effects on age-related liver steatosis remain unknown. Here we show that senescent liver cells indu...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44026-z |
| _version_ | 1797397912264638464 |
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| author | Jinjie Duan Wenhui Dong Guangyan Wang Wenjing Xiu Guangyin Pu Jingwen Xu Chenji Ye Xu Zhang Yi Zhu Chunjiong Wang |
| author_facet | Jinjie Duan Wenhui Dong Guangyan Wang Wenjing Xiu Guangyin Pu Jingwen Xu Chenji Ye Xu Zhang Yi Zhu Chunjiong Wang |
| author_sort | Jinjie Duan |
| collection | DOAJ |
| description | Abstract Aging is a major risk factor for metabolic disorders. Polyunsaturated fatty acid-derived bioactive lipids play critical roles as signaling molecules in metabolic processes. Nonetheless, their effects on age-related liver steatosis remain unknown. Here we show that senescent liver cells induce liver steatosis in a paracrine manner. Linoleic acid-derived 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE increase in middle-aged (12-month-old) and aged (20-month-old) male mouse livers and conditioned medium from senescent hepatocytes and macrophages. Arachidonate 15-lipoxygenase, an enzyme for 13-HODE and 9-HODE production, is upregulated in senescent cells. A 9-HODE and 13-HODE mixture induces liver steatosis and activates SREBP1. Furthermore, catalase (CAT) is a direct target of 13-HODE, and its activity is decreased by 13-HODE. CAT overexpression reduces 13-HODE-induced liver steatosis and protects male mice against age-related liver steatosis. Therefore, 13-HODE produced by senescent hepatocytes and macrophages activates SREBP1 by directly inhibiting CAT activity and promotes liver steatosis. |
| first_indexed | 2024-03-09T01:18:03Z |
| format | Article |
| id | doaj.art-dfc2a3621cbf413c9d67a8daa3b519d8 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T01:18:03Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-dfc2a3621cbf413c9d67a8daa3b519d82023-12-10T12:24:05ZengNature PortfolioNature Communications2041-17232023-12-0114111710.1038/s41467-023-44026-zSenescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activityJinjie Duan0Wenhui Dong1Guangyan Wang2Wenjing Xiu3Guangyin Pu4Jingwen Xu5Chenji Ye6Xu Zhang7Yi Zhu8Chunjiong Wang9NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical UniversityNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical UniversityNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical UniversityNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical UniversityNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical UniversityNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical UniversityHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical UniversityThe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical UniversityDepartment of Physiology and Pathophysiology, Tianjin Medical UniversityNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical UniversityAbstract Aging is a major risk factor for metabolic disorders. Polyunsaturated fatty acid-derived bioactive lipids play critical roles as signaling molecules in metabolic processes. Nonetheless, their effects on age-related liver steatosis remain unknown. Here we show that senescent liver cells induce liver steatosis in a paracrine manner. Linoleic acid-derived 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE increase in middle-aged (12-month-old) and aged (20-month-old) male mouse livers and conditioned medium from senescent hepatocytes and macrophages. Arachidonate 15-lipoxygenase, an enzyme for 13-HODE and 9-HODE production, is upregulated in senescent cells. A 9-HODE and 13-HODE mixture induces liver steatosis and activates SREBP1. Furthermore, catalase (CAT) is a direct target of 13-HODE, and its activity is decreased by 13-HODE. CAT overexpression reduces 13-HODE-induced liver steatosis and protects male mice against age-related liver steatosis. Therefore, 13-HODE produced by senescent hepatocytes and macrophages activates SREBP1 by directly inhibiting CAT activity and promotes liver steatosis.https://doi.org/10.1038/s41467-023-44026-z |
| spellingShingle | Jinjie Duan Wenhui Dong Guangyan Wang Wenjing Xiu Guangyin Pu Jingwen Xu Chenji Ye Xu Zhang Yi Zhu Chunjiong Wang Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity Nature Communications |
| title | Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity |
| title_full | Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity |
| title_fullStr | Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity |
| title_full_unstemmed | Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity |
| title_short | Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity |
| title_sort | senescence associated 13 hode production promotes age related liver steatosis by directly inhibiting catalase activity |
| url | https://doi.org/10.1038/s41467-023-44026-z |
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