Targeting Mitochondrial ROS-Mediated Ferroptosis by Quercetin Alleviates High-Fat Diet-Induced Hepatic Lipotoxicity.

Background: The protective effect of quercetin on nonalcoholic fatty liver disease (NAFLD) has been reported, but its mechanism remains poorly understood. Recently, quercetin was reported to be capable of inhibiting ferroptosis, which is a recognized type of regulated cell death. Moreover, hepatic ferroptosis plays an important role in the progression of NAFLD, but experimental evidence is limited. Hence, our study aimed to investigate the effect of quercetin on hepatic ferroptosis in high-fat diet (HFD)-induced NAFLD and further elucidate the underlying molecular mechanism. Methods: C57BL/6J mice were fed either a normal diet (ND), an HFD, or an HFD supplemented with quercetin for 12 weeks. Hepatic lipid peroxidation, steatosis, ferroptosis and iron overload were examined. In vitro, steatotic L-02 cells was used to study the potential mechanism. Results: We found that the HFD caused lipid peroxidation, lipid accumulation and ferroptosis in the liver, which were rescued by quercetin supplementation. Consistent with the in vivo results, quercetin alleviated lipid droplet accumulation and reduced the levels of lipid reactive oxygen species (ROS) and ferroptosis in steatotic L-02 cells. Using a mitochondrial ROS (MtROS) scavenger (Mito-TEMPO) and ferroptosis specific inhibitor (Fer-1), we found that quercetin remarkably alleviated lipid droplet accumulation and lipid peroxidation by reducing MtROS-mediated ferroptosis in steatotic L-02 cells. Conclusion: Our data showed that HFD consumption induced lipid accumulation and triggered ferroptosis in liver, ultimately leading to hepatic lipotoxicity, which can be alleviated by quercetin. Findings from this study provide new insight into the mechanism by which quercetin can be used for the prevention and treatment of NAFLD.

Maternal multivitamin supplementation is associated with a reduced risk of autism spectrum disorder in children: a systematic review and meta-analysis.

Several studies have explored the link of antenatal multivitamin supplementation with autism spectrum disorder (ASD) in offspring, but the findings are inconsistent. The purpose of the current study was to perform a systematic review and meta-analysis of published studies to evaluate the actual association between maternal multivitamin supplementation during the prenatal period and the risk of ASD in children. PubMed, EMBASE, PsycINFO, Web of Science, and Cochrane Library were searched up to August 26, 2018. The random-effects model was used to calculate the pooled results. The adjusted risk ratios (RRs) were used as the common measure of association among studies. Sensitivity and subgroup analyses were also conducted. A total of 5 articles (9 independent trials; 231 163 children encompassing 4459 cases) were included. The results of overall analysis showed that the likelihood of ASD in offspring whose mothers used multivitamin supplements during the prenatal period was significantly reduced compared with that in offspring of mothers without such supplementation (RR, 0.62; 95% CI, 0.45-0.86; P = .003). Additionally, the primary outcome of the meta-analysis was quite robust after being verified by sensitivity analyses and no publication bias was found. Furthermore, the findings of overall analysis were generally consistent with those of subgroup analyses. In conclusion, this meta-analysis supports a protective association between maternal multivitamin supplementation during the prenatal period and the subsequent risk of ASD in children. Further investigation is needed and should address the constituent(s) contributing to the protective effect of multivitamin on ASD risk and the underlying molecular mechanisms.

Green Tea Polyphenols Attenuate High-Fat Diet-Induced Renal Oxidative Stress through SIRT3-Dependent Deacetylation.

Fifty male Wistar rats were fed a standard chow diet or a high-fat (HF) diet, and different concentrations of green tea polyphenols (GTPs) (0.8, 1.6, and 3.2 g/L) were administered in the drinking water. We found that the malondialdehyde (MDA) level in the HF diet group was significantly higher than that in the control (CON) group (P<0.05). Decreased peroxisome proliferator-activated receptor (PPAR)-α and sirtuin 3 (SIRT3) expression, and increased manganese superoxide dismutase (MnSOD) acetylation levels were also detected in the HF diet group (P<0.05). GTP treatment upregulated SIRT3 and PPARα expression, increased the pparα mRNA level, reduced the MnSOD acetylation level, and decreased MDA production in rats fed a HF diet (P<0.05). No significant differences in total renal MnSOD and PPAR-γ coactivator-1α (PGC1-α) expression were detected. The reduced oxidative stress detected in kidney tissues after GTP treatment was partly due to the higher SIRT3 expression, which was likely mediated by PPARα.