backgroundCadmium (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.

methodsThis 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.

resultsThe 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/

conclusionsCollectively, 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.