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

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.PMID:37736721 | DOI:10.1186/s12944-023-01891-3

Source: Atherosclerosis - September 22, 2023 Category: Cardiology 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 Type: research