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.

In this study, PLA/TiO₂ composites materials were prepared via electrospinning and solution casting processes. By testing the mechanical properties, water contact angle, water vapor permeability, and solubility of the composite nanofibers and films, the comprehensive performances of the two types of nanocomposites were analyzed. The results show that maximum tensile strengths of 2.71 ± 0.11 MPa and 14.49 ± 0.13 MPa were achieved for the nanofibers and films at a TiO₂ content of 0.75 wt.%. Moreover, the addition of TiO₂ significantly cut down the water vapor transmittance rate of the nanofibers and films while significantly improving the water solubility. Further, the antibacterial activity increased under UV-A irradiation for a TiO₂ nanoparticle content of 0.75 wt.%, and the nanofiber and films exhibited inhibition zones of 4.86 ± 0.50 and 3.69 ± 0.40 mm for E. coli, and 5.98 ± 0.77 and 4.63 ± 0.45 mm for S. aureus, respectively. Overall, the performance of the nanofiber was better than that of the film. Nevertheless, both the nanocomposite membranes satisfied the requirements of food packaging materials.

With the prevalence of obesity all over the world, human health has been seriously affected. In particular, the number of diabetic and cardiovascular diseases has increased dramatically. The herb Coreopsis tinctoria (C. tinctoria) shows diverse biological and pharmacological activities, which are mainly attributed to its flavonoids. However, the specific functional substances that play an active role in C. tinctoria remain unclear, and its mechanism has not been deeply explored. In this study, we established a diet-induced obesity (DIO) mice model and treated mice with C. tinctoria or kaempferol for 8 weeks. The results showed that both C. tinctoria and kaempferol lowered body weight, reduced fasting blood glucose, and improved glucose tolerance and insulin resistance to alleviate obesity in DIO mice. The level of hemoglobin A1c also decreased significantly after treatment with C. tinctoria and kaempferol. Moreover, the administration of C. tinctoria and kaempferol also restored gut microbiota imbalance and significantly increased Desulfovibrio and Butyricimonas levels, which have been reported to improve glucose metabolism and intestinal health. In general, our study shows that C. tinctoria is a potential hypoglycemic substance for obesity and may reduce blood glucose by regulating gut microbiota, and that kaempferol is one of the effective substances of C. tinctoria.

Aging is a major cause of bone loss and osteoporosis. Diallyl trisulfide (DATS), one of the main organic sulfides in garlic oil, has been shown to alleviate arthritis in mice. However, further research is still needed to determine how DATS affects bone formation and bone loss in aging mice. Here, we established a mouse model of natural aging for dietary DATS intervention. DATS treatment improved the bone microstructure, including the disorganized arrangement of bone trabeculae and promoted collagen synthesis, as confirmed by micro-CT and histological analyses. The abundance of beneficial bacteria for bone formation, such as Clostridiaceae and Erysipelotrichaceae, and the microbial diversity and community richness were all altered by DATS, according to 16S rRNA sequencing data. 14 potential biomarkers and 9 important metabolic pathways were examined using serum metabolomics analysis. Additionally, there has been a significant reduction in sphingosine, which is directly associated with bone metabolism. The level of sphingosine and relative abundance of Clostridium were found to be negatively correlated by correlation analysis, indicating that bacteria may regulate bone reconstruction via influencing metabolites. Furthermore, Runx2 and β-catenin gene expression levels increased in bones, which may be related to the ameliorative mechanism of DATS. Our results suggested that DATS may prevent age-related bone loss by upregulating osteogenic gene expression through altering gut microbes and serum metabolism.

Nanozymes with antioxidant and anti-inflammatory properties can alleviate drug-induced acute liver injury.

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASLD) represents a prevalent liver disease worldwide. It is crucial to maintain the stability of the gut–liver axis in order to inhibit the advancement of MASLD. Broccoli-derived exosome-like nanoparticles (BDENs) can alleviate constipation and improve colitis. This study investigated whether BDENs possess therapeutic potential for improving induced MASLD by the gut–liver axis. Methods: BDENs were fractionated from fresh broccoli using differential centrifugation, and the microRNAs were identified and analyzed. 24 male C57BL/6J mice (6 weeks old) were randomized into the control group, HFD group, and BDENs group, with 8 mice per group. After 8 weeks of high-fat diet modeling, the BDENs group accepted BDENs daily oral gavage of 100 mg/kg (B.W.), while the control and HFD groups accepted 1 × PBS. Four weeks after BDENs intervention, analysis was conducted on liver injury markers, liver tissue pathology, intestinal barrier, cecal content metabolomics and fecal 16S rRNA, serum inflammatory factors, and hepatic inflammation. Results: BDENs identified 1659 miRNAs associated with physiological processes such as immunity, antioxidant defense, and fatty acid biosynthesis. BDENs significantly reduced weight and ALT/AST ratio (p < 0.05). Furthermore, BDENs attenuated hepatic histopathological damage and lipid accumulation. For the gut–liver axis, BDENs maintained intestinal barrier, regulated intestinal bile acid metabolism and restored the gut microbiota. Additionally, BDENs reduced serum LPS level (p < 0.01) and suppressed hepatic inflammation, including F4/80 and IL-6, IL-1β (p < 0.0001). Conclusions: Oral BDENs therapy demonstrates potential for ameliorating MASLD.