• Yang-Ting Dong, Kun Cao, Jie Xiang, Xiao-Lan Qi, Yan Xiao, Wen-Feng Yu, Yan He, Wei Hong, and Zhi-Zhong Guan.
• Key Laboratory of Endemic and Ethnic Diseases (Guizhou Medical University) of the Ministry of Education and Provincial Key Laboratory of Medical Molecular Biology, Guiyang 550004, PR China; Department of Pathology at the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, PR China.
• Neuroscience. 2023 Jun 15; 521: 134147134-147.

AbstractTo examine whether resveratrol (RSV), an activator of silent mating-type information regulation 2 homolog 1 (SIRT1), can reverse the disruption of lipid metabolism caused by β-amyloid peptide (Aβ), APP/PS1 mice or cultured primary rat neurons were treated with RSV, suramin (inhibitor of SIRT1), ZLN005, a stimulator of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), or PGC-1α silencing RNA. In the brains of the APP/PS1 mice, expressions of SIRT1, PGC-1α, low-density lipoprotein receptor (LDLR) and very LDLR (VLDLR) were reduced at the protein and, in some cases, mRNA levels; while the levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein E (ApoE), total cholesterol and LDL were all elevated. Interestingly, these changes were reversed by administration of RSV, while being aggravated by suramin. Furthermore, activation of PGC-1α, but inhibition of SIRT1, decreased the levels of PCSK9 and ApoE, while increased those of LDLR and VLDLR in the neurons exposed to Aβ, and silencing PGC-1α, but activation of SIRT1, did not influence the levels of any of these proteins. These findings indicate that RSV can attenuate the disruption of lipid metabolism observed in the brains of APP mice and in primary neurons exposed to Aβ by activating SIRT1, in which the mechanism may involve subsequently affecting PGC-1α.Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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