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Sirt6 enhances macrophage lipophagy and improves lipid metabolism disorder by regulating the Wnt1/β-catenin pathway in atherosclerosis

Authors :
Tingting Wang
Zheng Cheng
Ran Zhao
Jin Cheng
He Ren
Pengke Zhang
Pengyun Liu
Qimeng Hao
Qian Zhang
Xiaolei Yu
Dongdong Sun
Dongwei Zhang
Source :
Lipids in Health and Disease, Vol 22, Iss 1, Pp 1-15 (2023)
Publication Year :
2023
Publisher :
BMC, 2023.

Abstract

Abstract Lipid metabolism disorders are considerably involved in the pathology of atherosclerosis; nevertheless, the fundamental mechanism is still largely unclear. This research sought to examine the function of lipophagy in lipid metabolism disorder-induced atherosclerosis and its fundamental mechanisms. Previously, Sirt6 has been reported to stimulate plaque stability by promoting macrophage autophagy. However, its role in macrophage lipophagy and its relationship with Wnt1 remains to be established. In this study, ApoE−/−: Sirt6−/− and ApoE−/−: Sirt6Tg mice were used and lipid droplets were analysed via transmission electron microscopy and Bodipy 493/503 staining in vitro. Atherosclerotic plaques in ApoE−/−: Sirt6−/− mice showed greater necrotic cores and lower stability score. Reconstitution of Sirt6 in atherosclerotic mice improved lipid metabolism disorder and prevented the progression of atherosclerosis. Furthermore, macrophages with Ac-LDL intervention showed more lipid droplets and increased expression of adipophilin and PLIN2. Reconstitution of Sirt6 recruited using SNF2H suppressed Wnt1 expression and improved lipid metabolism disorder by promoting lipophagy. In addition, downregulation of Sirt6 expression in Ac-LDL-treated macrophages inhibited lipid droplet degradation and stimulated foam cell formation. Innovative discoveries in the research revealed that atherosclerosis is caused by lipid metabolism disorders due to downregulated Sirt6 expression. Thus, modulating Sirt6’s function in lipid metabolism might be a useful therapeutic approach for treating atherosclerosis.

Details

Language :
English
ISSN :
1476511X
Volume :
22
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Lipids in Health and Disease
Publication Type :
Academic Journal
Accession number :
edsdoj.5f57f8ae5e3447e7a09cc34fe42bb91e
Document Type :
article
Full Text :
https://doi.org/10.1186/s12944-023-01891-3