This meta-analysis suggests that higher SUA levels led to an increased risk of MS regardless of the study characteristics, and were consistent with a linear dose-response relationship. In addition, SUA was also a causal factor for the NAFLD risk.

Background FAT4 functions as a tumor suppressor, and previous findings have demonstrated that FAT4 can inhibit the epithelial-to-mesenchymal transition (EMT) and the proliferation of gastric cancer cells. However, few studies have investigated the role of FAT4 in the development of colorectal cancer (CRC). The current study aimed to detect the role of FAT4 in the invasion, migration, proliferation and autophagy of CRC and elucidate the probable molecular mechanisms through which FAT4 interacts with these processes. Methods Transwell invasion assays, MTT assays, transmission electron microscopy, immunohistochemistry and western blotting were performed to evaluate the migration, invasion, proliferation and autophagy abilities of CRC cells, and the levels of active molecules involved in PI3K/AKT signaling were examined through a western blotting analysis. In addition, the function of FAT4 in vivo was assessed using a tumor xenograft model. Results FAT4 expression in CRC tissues was weaker than that in nonmalignant tissues and could inhibit cell invasion, migration, and proliferation by promoting autophagy in vitro. Furthermore, the regulatory effects of FAT4 on autophagy and the EMT were partially attributed to the PI3K-AKT signaling pathway. The results in vivo also showed that FAT4 modulated CRC tumorigenesis. Conclusion FAT4 can regulate the activity of PI3K to promote autophagy and inhibit the EMT in part through the PI3K/AKT/mTOR and PI3K/AKT/GSK-3β signaling pathways.

Dysfunction of β-cell is one of major characteristics in the pathogenesis of type 2 diabetes. The combination of obesity and type 2 diabetes, characterized as ‘diabesity’, is associated with elevated plasma free fatty acids (FFAs). Oxidative stress has been implicated in the pathogenesis of FFA-induced β-cell dysfunction. However, molecular mechanisms linking between reactive oxygen species (ROS) and FFA-induced β-cell dysfunction and apoptosis are less clear. In the present study, we test the hypothesis that NOX2-derived ROS may play a critical role in dysfunction and apoptosis of β-cells induced by FFA. Our results show that palmitate and oleate (0.5 mmol/L, 48 h) induced JNK activation and AKT inhibition which resulted in decreased phosphorylation of FOXO1 following nuclear localization and the nucleocytoplasmic translocation of PDX-1, leading to the reducing of insulin and ultimately dysfunction of pancreatic NIT-1 cells. We also found that palmitate and oleate stimulated apoptosis of NIT-1 cells through p38MAPK, p53 and NF-κB pathway. More interestingly, our data suggest that suppression of NOX2 may restore FFA-induced dysfunction and apoptosis of NIT-1 cells. Our findings provide a new insight of the NOX2 as a potential new therapeutic target for preservation of β-cell mass and function.

Background Gut bacteria Akkermansia has been shown an anti-obesity protective effect in previous studies and may be used as promising probiotics. However, the above effect may be confounded by common factors, such as sex, age and diets, which should be verified in a generalized population. Methods We used datasets from the American Gut Project to strictly reassess the association and further examined the effect of aging on it. A total of 10,534 participants aged 20 to 99 years from the United States and the United Kingdom were included. The relative abundance of Akkermansia was assessed based on 16S rRNA sequencing data. Obesity (body mass index, BMI ≥ 30 kg/m2) risks were compared across Akkermansia quintiles in logistic models with adjustment for common confounders. Restricted cubic splines were used to examine dose response effects between Akkermansia, obesity and age. A sliding-windows-based algorithm was used to investigate the effect of aging on Akkermansia-obesity associations. Results The median abundance of Akkermansia was 0.08% (interquartile range: 0.006–0.93%), and the prevalence of obesity was 11.03%. Nonlinear association was detected between Akkermansia and obesity risk (P = 0.01). The odds ratios (95% confidence interval) for obesity across the increasing Akkermansia quintiles (referencing to the first quintile) were 1.14 (0.94–1.39), 0.94 (0.77–1.15), 0.70 (0.56–0.85) and 0.79 (0.64–0.96) after adjusting for age and sex (P for trend < 0.001). This association remained unchanged after further controlling for smoking, alcohol drinking, diet, and country. The odds ratios (95% CI) of Akkermansia were 0.19 (0.03–0.62) and 0.77 (0.64–0.91) before and over 40 years, respectively, indicating that the protective effect of Akkermansia against obesity was not stable with aging. Conclusion High relative abundance of Akkermansia is associated with low risk of obesity and the association declines with aging.