{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T03:42:01Z","timestamp":1788320521961,"version":"build-2803163510"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>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\u03b1 (HIF-1\u03b1) 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.<\/jats:p>","DOI":"10.3389\/fnins.2022.978431","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T07:33:40Z","timestamp":1663313620000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["A long-term high-fat diet influences brain damage and is linked to the activation of HIF-1\u03b1\/AMPK\/mTOR\/p70S6K signalling"],"prefix":"10.3389","volume":"16","author":[{"given":"Fei","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-min","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-yuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-hao","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-you","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.neubiorev.2019.08.010","article-title":"The effect of high fat, high sugar, and combined high fat-high sugar diets on spatial learning and memory in rodents: a meta-analysis.","volume":"107","author":"Abbott","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/j.1365-2362.2009.02086.x","article-title":"Early atherosclerosis and vascular inflammation in mice with diet-induced type 2 diabetes.","volume":"39","author":"Bartels","year":"2009","journal-title":"Eur. J. Clin. Invest."},{"key":"B3","doi-asserted-by":"publisher","first-page":"S55","DOI":"10.1038\/ijo.2008.124","article-title":"The regulation of AMP-activated protein kinase by upstream kinases.","volume":"32","author":"Carling","year":"2008","journal-title":"Int. J. Obes."},{"key":"B4","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.fertnstert.2015.05.020","article-title":"Dienogest enhances autophagy induction in endometriotic cells by impairing activation of AKT, ERK1\/2, and mTOR.","volume":"104","author":"Choi","year":"2015","journal-title":"Fertil. Steril."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065367","article-title":"Induction of autophagy by a novel small molecule improves abeta pathology and ameliorates cognitive deficits.","volume":"8","author":"Chu","year":"2013","journal-title":"PLoS One"},{"key":"B6","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nn1372","article-title":"Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function.","volume":"8","author":"Cleary","year":"2005","journal-title":"Nat. Neurosci."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.318","article-title":"Impaired autophagosome clearance contributes to neuronal death in a piglet model of neonatal hypoxic-ischemic encephalopathy.","volume":"8","author":"Cui","year":"2017","journal-title":"Cell Death Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1093\/molbev\/msx083","article-title":"Detection of pathways affected by positive selection in primate lineages ancestral to humans.","volume":"34","author":"Daub","year":"2017","journal-title":"Mol. Biol. Evol."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k2139","article-title":"Dietary fat and cardiometabolic health: evidence, controversies, and consensus for guidance.","volume":"361","author":"Forouhi","year":"2018","journal-title":"BMJ"},{"key":"B10","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/s41580-018-0033-y","article-title":"Autophagy as a promoter of longevity: insights from model organisms.","volume":"19","author":"Hansen","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ceb.2014.09.004","article-title":"AMPK: positive and negative regulation, and its role in whole-body energy homeostasis.","volume":"33","author":"Hardie","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"B12","first-page":"24","article-title":"The metabolic syndrome.","author":"Hoffman","year":"2015","journal-title":"S D Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"901","DOI":"10.2337\/db06-0911","article-title":"Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation.","volume":"56","author":"Hosogai","year":"2007","journal-title":"Diabetes"},{"key":"B14","doi-asserted-by":"publisher","first-page":"5335","DOI":"10.1172\/JCI63562","article-title":"Rho-kinase\/AMPK axis regulates hepatic lipogenesis during overnutrition.","volume":"128","author":"Hu","year":"2018","journal-title":"J. Clin. Invest."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1016\/j.neurobiolaging.2014.02.010","article-title":"High-fat diet-induced memory impairment in triple-transgenic Alzheimer\u2019s disease (3xTgAD) mice is independent of changes in amyloid and tau pathology.","volume":"35","author":"Knight","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"B16","doi-asserted-by":"publisher","first-page":"F414","DOI":"10.1152\/ajprenal.00463.2014","article-title":"Interactions between HIF-1alpha and AMPK in the regulation of cellular hypoxia adaptation in chronic kidney disease.","volume":"309","author":"Li","year":"2015","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1172\/JCI33585","article-title":"The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice.","volume":"118","author":"Pickford","year":"2008","journal-title":"J. Clin. Invest."},{"key":"B18","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1046\/j.1467-789x.2003.00117.x","article-title":"Fast foods, energy density and obesity: a possible mechanistic link.","volume":"4","author":"Prentice","year":"2003","journal-title":"Obes. Rev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1089\/ars.2017.7280","article-title":"Uncoupled endothelial nitric oxide synthase enhances p-tau in chronic traumatic encephalopathy mouse model.","volume":"30","author":"Shin","year":"2019","journal-title":"Antioxid Redox Signal."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.646924","article-title":"Cellular senescence in brain aging.","volume":"13","author":"Sikora","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1165\/rcmb.2009-0415OC","article-title":"Hyperoxia-induced LC3B interacts with the Fas apoptotic pathway in epithelial cell death.","volume":"46","author":"Tanaka","year":"2012","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22168-2","article-title":"Skeletal muscle transcriptome in healthy aging.","volume":"12","author":"Tumasian","year":"2021","journal-title":"Nat. Commun."},{"key":"B23","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/416535a","article-title":"Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo.","volume":"416","author":"Walsh","year":"2002","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/978-981-15-0602-4_3","article-title":"Regulation of autophagy by mTOR signaling pathway.","volume":"1206","author":"Wang","year":"2019","journal-title":"Adv. Exp. Med. Biol."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.978431\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T07:33:42Z","timestamp":1663313622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.978431\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,16]]},"references-count":24,"alternative-id":["10.3389\/fnins.2022.978431"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2022.978431","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,16]]},"article-number":"978431"}}