Obesity is associated with impaired intestinal barrier function and dysbiosis of the gut microbiota. Spermidine, a polyamine that acts as an autophagy inducer, has important benefits in patients with aging-associated diseases and metabolic dysfunction. However, the mechanism of spermidine on obesity remains unclear. Here, we show that spermidine intake is negatively correlated with obesity in both humans and mice. Spermidine supplementation causes a significant loss of weight and improves insulin resistance in diet-induced obese (DIO) mice. These effects are associated with the alleviation of metabolic endotoxemia and enhancement of intestinal barrier function, which might be mediated through autophagy pathway and TLR4-mediated microbial signaling transduction. Moreover, spermidine causes the significant alteration of microbiota composition and function. Microbiota depletion compromises function, while transplantation of spermidine-altered microbiota confers protection against obesity. These changes might partly be driven by an SCFAproducing bacterium, Lachnospiraceae NK4A136 group, which was decreased in obese subjects and subsequently increased by spermidine. Notably, the change of Lachnospiraceae NK4A136 group is significantly correlated with enhanced gut barrier function induced by spermidine. Our results indicate that spermidine supplementation may serve as a viable therapy for obesity.
novel PFOS alternatives, 6:2 chlorinated polyfluorinated ether
sulfonate (F-53B) and sodium p-perfluorous nonenoxybenzenesulfonate
(OBS), are emerging in the Chinese market, but little is known about
their ecological risks. In this study, zebrafish embryos were exposed
to PFOS, F-53B, and OBS to evaluate their bioconcentration and acute
metabolic consequences. Per- and polyfluoroalkyl substances (PFASs)
accumulated in larvae in the order of F-53B > PFOS > OBS, with
bioconcentration factors ranging from 20 to 357. Exposure to F-53B
and PFOS, but not OBS, increased energy expenditure, and reduced feed
intake in a concentration-dependent manner and the expression of genes
involved in metabolic pathways at the transcriptional and translational
levels. Molecular docking revealed that the binding affinities of
PFASs to glucokinase were decreased in the following order: F-53B
> PFOS > OBS. Finally, the results of Point of Departure (PoD)
that metabolic end points at the molecular and organismal level are
most sensitive to F-53B followed by PFOS and OBS. Collectively, F-53B
has the highest bioconcentration potential and the strongest metabolism-disrupting
effects, followed by PFOS and OBS. Our findings have important implications
for the assessment of early developmental metabolic effects of PFOS
alternatives F-53B and OBS in wildlife and humans.
The fungicide imazalil (IMZ) is widely used to prevent and treat fungal diseases in plants and animals. Here, male adult C57BL/6 mice were exposed to 0.1, 0.5, and 2.5 mg/kg body weight IMZ for 2, 5, or 15 weeks. The microbiota in cecal contents and feces changed during chronic IMZ exposure at phylum and genus levels. Sequencing of the V3-V4 region of the bacterial 16S rRNA gene revealed a significant change in the richness of microbiota in cecal contents and feces after exposure to 2.5 mg/kg IMZ for 15 weeks. Operational taxonomic unit (OTU) analysis indicated that 31.1% of cecal OTUs and 14.0% of fecal OTUs changed after IMZ exposure. In addition, chronic IMZ exposure also disturbed the intestinal barrier function of the mice, reducing mucus secretion, decreasing the expression of cystic fibrosis transmembrane conductance regulator (CFTR)-related genes in both the ileum and colon. Molecular docking analysis revealed that key hydrogen bonds were formed by nitrogen atoms of the imidazole bond with Val440 of CFTR and Ala697 of the SLC26 family. Our data suggested that gut microbiota and intestinal barrier were potential toxicological targets of IMZ.
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