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A long-term high-fat diet influences brain damage and is linked to the activation of HIF-1 alpha/AMPK/mTOR/p70S6K signalling
Chen, Fei1,2,3,4,5; Yi, Wen-Min1,2,3,4,5; Wang, Sheng-Yuan1,2,3,4,5; Yuan, Ming-Hao1,2,4,5; Wen, Jie5,6; Li, Hong-Yan5,7; Zou, Qian4,5; Liu, Shu1,2,3,4,5; Cai, Zhi-You1,2,3,4,5
2022-09-16
摘要High-fat diets (HFDs) are related to the incidence of obesity and diabetes, but the effect of high-fat diet-induced brain damage remains to be clarified. In our study, we found that 24 weeks of a HFD effectively induced obesity and a change in fur color in mice. In addition, the mice also exhibited deficits in learning and memory. We further found that autophagic flux was impaired in mice after HFD feeding. Hypoxia-inducible factor 1 alpha (HIF-1 alpha) expression was significantly increased in HFD-fed mice, and HFD feeding inhibited adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and induced mechanistic target of rapamycin (mTOR) phosphorylation and p70S6K expression. Treatment of HFD-induced BV2 cell model with palmitic acid (PA) was used to further verify a similar result. We concluded that improving tissue hypoxia or enhancing autophagy through the AMPK/mTOR/p70S6K pathway may be a relevant strategy for improving obesity- and ageing-related disorders.
关键词ageing obesity high-fat (HF) diet autophagy HIF-1 alpha AMPK m TOR pathway
DOI10.3389/fnins.2022.978431
发表期刊FRONTIERS IN NEUROSCIENCE
卷号16页码:13
通讯作者Cai, Zhi-You(caizhiyou@ucas.ac.cn)
收录类别SCI
WOS记录号WOS:000862694300001
语种英语