{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:29Z","timestamp":1787029289010,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","award":["E2E43202X2"],"award-info":[{"award-number":["E2E43202X2"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder associated with impaired lipid metabolism and oxidative stress. As a natural antioxidant and dithiol compound, \u03b1-lipoic acid (ALA) may play a beneficial role in modulating hepatic metabolism. This study investigates the potential mechanisms through which ALA may alleviate NAFLD. Methods: To construct an NAFLD model, NCTC 1469 cells were exposed to oleic acid and palmitic acid (OA\/PA) and glucose for 24 h. RT-qPCR, Western blotting, and siRNA analyses were used to examine the effects and mechanisms of ALA. In vivo, C57BL\/6J mice were fed a high-fat diet for 11 weeks and treated with ALA (200 mg\/kg\/day, intragastrical) for 4 weeks to evaluate its impact on NAFLD. Results: In NCTC 1469 cells exposed to OA\/PA and glucose, ALA markedly reduced lipid accumulation by activating TFEB, which in turn promoted fatty acid \u03b2-oxidation and chaperone-mediated autophagy (CMA). Furthermore, ALA activated NRF2-dependent CMA and mitigated oxidative stress. Inhibition of AMPK or silencing of TFEB\/NRF2 abolished these effects, indicating the key role of the AMPK\u2013TFEB\/NRF2 axis. In HFD-fed mice, ALA alleviated hepatic steatosis, serum lipid abnormalities, and liver injury, consistent with its activation of CMA and \u03b2-oxidation and reduction in oxidative stress via this pathway. Conclusions: ALA synchronously activates CMA, \u03b2-oxidation, and antioxidant responses via a unified AMPK pathway to reduce lipid accumulation and oxidative stress, providing a mechanistically integrated therapeutic strategy for NAFLD.<\/jats:p>","DOI":"10.3390\/nu18030402","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T11:14:07Z","timestamp":1769426047000},"page":"402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["\u03b1-Lipoic Acid Alleviates Non-Alcoholic Fatty Liver Disease by Elevating Chaperone-Mediated Autophagy and Increasing \u03b2-Oxidation via AMPK-TFEB Axis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2041-3984","authenticated-orcid":false,"given":"Keting","family":"Dong","sequence":"first","affiliation":[{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3498-3049","authenticated-orcid":false,"given":"Miao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Bai","sequence":"additional","affiliation":[{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3939-6471","authenticated-orcid":false,"given":"Jianhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.14218\/JCTH.2020.00014","article-title":"NAFLD Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications and the Trends in the United States","volume":"8","author":"Gadiparthi","year":"2020","journal-title":"J. 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