Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity.

Autor: Duan J; NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.; Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China.; School of Public Health, Tianjin Medical University, Tianjin, China., Dong W; NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.; Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China., Wang G; NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.; Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China.; The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, China., Xiu W; NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.; Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China., Pu G; NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.; Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China., Xu J; NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.; Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China., Ye C; Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China., Zhang X; The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, China. xuzhang@tmu.edu.cn., Zhu Y; Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China. zhuyi@tmu.edu.cn.; The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, China. zhuyi@tmu.edu.cn., Wang C; NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. wangchunjiong@tmu.edu.cn.; Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China. wangchunjiong@tmu.edu.cn.; Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, China. wangchunjiong@tmu.edu.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Dec 09; Vol. 14 (1), pp. 8151. Date of Electronic Publication: 2023 Dec 09.
DOI: 10.1038/s41467-023-44026-z
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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