{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:05:22Z","timestamp":1790139922530,"version":"4.0.1"},"reference-count":72,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Scientific Research Project of Higher Education Institutions in Henan Province","award":["27BQ210002"],"award-info":[{"award-number":["27BQ210002"]}]},{"name":"Key Scientific Research Project of Higher Education Institutions in Henan Province","award":["27A550006"],"award-info":[{"award-number":["27A550006"]}]},{"name":"Key Laboratory of Food Nutrition and Functional Food of Hainan Province","award":["KF202509"],"award-info":[{"award-number":["KF202509"]}]},{"name":"Science and Technology R&D Program Joint Fund of Henan Province","award":["235200810019"],"award-info":[{"award-number":["235200810019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Cadmium (Cd) exposure impairs the autophagic response, a core mechanism for cell preservation and organismal homeostasis, eventually resulting in metabolic disturbances, mitochondrial dysfunction, and oxidative stress. L-theanine (LT) exhibits multiple health benefits with a high safety profile. However, the effects of LT on Cd exposure-induced impairments in autophagy and autophagy-related physiological functions remain unclear. Methods: This study investigated the effects of LT on the survival time of mice acutely exposed to Cd and the regulating effect of LT on autophagy and subsequent metabolic dysfunction in mice subjected to subchronic Cd exposure. Results: The results showed that acute Cd exposure resulted in 100% mortality within 8 h. However, LT treatment significantly prolonged the median survival time of mice from 4 h to 16 h and reduced the mortality to 60%. In the context of subchronic Cd exposure, autophagy was inhibited, as evidenced by the downregulation of the AMPK\/mTOR signaling pathway mediated by DPP-4 and SIRT1. This exposure also promoted lipid peroxidation and ferroptosis, indicated by the inactivation of the AMPK\/p-ACC axis and marked alterations in ferroptosis markers. Furthermore, mitochondrial dysfunction was suggested by the downregulation of the SIRT1\/PGC-1\u03b1\/Nrfs\/TFAM signaling pathway and reductions in COX and SDH activities. Additionally, glucolipid metabolism was impaired, as indicated by the downregulation of the AMPK and PI3K\/AKT signaling pathways and elevated lipid and glycogen accumulation in the liver of mice. LT significantly decreased the level of DPP-4 and upregulated SIRT1, leading to the activation of AMPK. This activation restored autophagy response by downregulating mTOR, promoted energy homeostasis by reducing lipid biosynthesis and enhancing fatty acid oxidation, blocked lipid peroxidation and ferroptosis through the phosphorylation of ACC at the serine 79 site and reducing the ubiquitination-mediated degradation of GPX4, and maintained mitochondrial function by upregulating the PGC-1\u03b1\/Nrfs\/TFAM signaling pathway. Conclusions: Collectively, LT effectively ameliorates mitochondrial dysfunction, ferroptosis and glucolipid dysmetabolism in Cd-exposed mice, and these effects are accompanied by findings consistent with modulation of autophagy-related signaling in the liver.<\/jats:p>","DOI":"10.3390\/nu18183098","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:50:03Z","timestamp":1789995003000},"page":"3098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["L-Theanine Prevents Autophagy Impairment to Counteract Cadmium-Induced Hepatic Mitochondrial Dysfunction, Ferroptosis, and Glucolipid Dysmetabolism in Mice"],"prefix":"10.3390","volume":"18","author":[{"given":"Qiuyan","family":"Ban","sequence":"first","affiliation":[{"name":"Department of Tea Science, College of Horticulture, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Wenjing","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Tea Science, College of Horticulture, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Qiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Tea Science, College of Horticulture, Henan Agricultural University, Zhengzhou 450046, 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