Day and Night Reversed Feeding Aggravates High-Fat Diet-Induced Abnormalities in Intestinal Flora and Lipid Metabolism in Adipose Tissue of Mice.

BACKGROUND: The incongruity between dietary patterns and the circadian clock poses an elevated risk for metabolic health issues, particularly obesity and associated metabolic disorders. The intestinal microflora engages in regulating various physiological functions of the host through its metabolites. OBJECTIVES: This study aimed to investigate the impact of reversed feeding schedules during the day and night on intestinal flora and lipid metabolism in high-fat diet-induced obese mice. METHODS: Mice aged 8-10 wk were subjected to either daytime or nighttime feeding and were administered a control or high-fat diet for 18 wk. At the end of the experiment, various assessments were conducted, including analysis of serum biochemic indices, histologic examination, evaluation of gene and protein expression in adipose tissue, and scrutiny of changes in intestinal microbial composition. RESULTS: The results showed that day-night reversed feeding caused an increase in fasting blood glucose and exacerbated the high-fat diet-induced weight gain and lipid abnormalities. The mRNA expression levels of Leptin and Dgat1 were increased by day-night reversed feeding, which also reduced the expression level of adiponectin under the high-fat diet. Additionally, there was a significant increase in the protein concentrations of PPARγ, SREBP1c, and CD36. Inverted feeding schedules led to a reduction in intestinal microbial diversity, an increase in the abundance of inflammation-related bacteria, such as Coriobacteriaceae_UCG-002, and a suppression of beneficial bacteria, including Akkermansia, Candidatus_Saccharimonas, Anaeroplasma, Bifidobacterium, Carnobacterium, and Odoribacter. Acinetobacter exhibited a significant negative correlation with Leptin and Fasn, suggesting potential involvement in the regulation of lipid metabolism. CONCLUSIONS: The results elucidated the abnormalities of lipid metabolism and intestinal flora caused by day-night reversed feeding, which exacerbates the adverse effects of a high-fat diet on lipid metabolism and intestinal microflora. This reversal in feeding patterns may disrupt both intestinal and lipid metabolism homeostasis by altering the composition and abundance of intestinal microflora in mice.

Biothiol-triggered, self-disassembled silica nanobeads for intracellular drug delivery.

Silica-based nanomaterials have demonstrated great potential in biomedical applications due to their chemical inertness. However, the degradability and endosomal trapping issues remain as rate-limiting barriers during their innovation. In this study, we provide a simple yet novel sol-gel approach to construct the redox-responsive silica nanobeads (ReSiNs), which could be rapidly disassembled upon redox gradient for intracellular drug delivery. The disulfide-linked scaffold of the nanobead was synthesized by employing the dithiobis-(succinimidyl propionate) to bridge (3-aminopropyl)-trimethoxysilane. Such silica matrix could be efficiently disrupted in response to intracellular glutathione, resulting in drug release and collapse of entire nanocarrier. Moreover, the ReSiNs exhibited insignificant cytotoxicity before and after the degradation. These results indicated the potential of using ReSiNs as a novel silica-based, biothiol-degradable nanoplatform for future drug delivery.