Zearalenone, a mycotoxin produced by fungi of the genus Fusarium, widely exists in animal feed and human food. The structure of zearalenone is similar to estrogen, so it mainly has estrogenic effects on various organisms. Products contaminated with zearalenone can pose risks to animals and humans. Therefore, it is imperative to carry out toxicological research on zearalenone and evaluate its risk to human health. This paper briefly introduces the production, physical, and chemical properties of zearalenone and the research progress of its toxicity kinetics, focusing on its genetic toxicity, reproductive toxicity, hepatotoxicity, immunotoxicity, carcinogenicity, endocrine interference, and its impact on intestinal health. Finally, the progress of the risk assessment of human exposure is summarized to provide a reference for the follow-up study of zearalenone.

Background and Aims: NAFLD has become a major metabolic disease worldwide. A few studies have reported the potential relationship between mitochondrial pyruvate carrier 1 (MPC1) and inflammation, fibrosis, and insulin sensitivity in obese or NASH mouse models. However, the impact of MPC1 on NAFLD-related liver lipid metabolism and its role in the NAFLD progression require further investigation. Approach and Results: MPC1 expression was measured in liver tissues from normal controls and patients with NAFLD. We characterized the metabolic phenotypes and expression of genes involved in hepatic lipid accumulation in MPC1 systemic heterozygous knockout (MPC1^+/−) mice. Hepatic protein lactylation was detected using Tandem Mass Tags proteomics and verified by the overexpression of lactylation mutants in cells. Finally, the effect of MPC1 inhibition on liver inflammation was examined in mice and AML-12 cells. Here, we found that MPC1 expression was positively correlated to liver lipid deposition in patients with NAFLD. MPC1^+/− mice fed with high-fat diet had reduced hepatic lipid accumulation but no change in the expression of lipid synthesis-related genes. MPC1 knockout affected the lactylation of several proteins, especially fatty acid synthase, through the regulation of lactate levels in hepatocytes. Lactylation at the K673 site of fatty acid synthase inhibited fatty acid synthase activity, which mediated the downregulation of liver lipid accumulation by MPC1. Moreover, although MPC1 knockout caused lactate accumulation, inflammation level was controlled because of mitochondrial protection and macrophage polarization. Conclusions: In NAFLD, MPC1 levels are positively correlated with hepatic lipid deposition; the enhanced lactylation at fatty acid synthase K673 site may be a downstream mechanism.

The increased prevalence of obesity significantly affects human health worldwide. Improvement of glycometabolism by dietotherapy/herbal remedy is an effective approach to ameliorate obesity. In this study, high-fat-diet induced obese (DIO) mice were treated with mulberry leaves for 13 weeks. The results showed that mulberry leaves significantly alleviated adiposity of DIO mice including reducing body weight gain, fat accumulation and fasting blood glucose, and improving insulin sensitivity. In addition, mulberry leaves had protective effects on liver and kidneys. The abundant flavonoids, polyphenols and 1-deoxynojirimycin in mulberry leaves were likely responsible for their beneficial effects. Mechanistically, we found that mulberry leaves could alleviate obesity by enhancing brown adipose tissue (BAT) activity partly indicated by elevated thermogenesis and overexpression of uncoupling protein 1 in BAT. Moreover, mulberry leaves significantly increased the Bacteroidetes/Firmicutes ratio and Akkermansia level that were closely associated with obesity development and progression, and decreased the potential proinflammatory Proteobacteria in feces. These findings reveal that the mulberry leaf is an edible plant food with therapeutic potential for obesity and may provide dietotherapy/herbal remedy to the treatment of obesity and its complications.