The influence of
pollutants on
metabolic diseases such as
type 2 diabetes mellitus is an emerging field in environmental medicine. Here, we explored the effects of a low-dose
endosulfan sulfate (ES), a major metabolite of the
pesticide endosulfan and a bio-persistent contaminant detected in environmental and human samples, on the progress of
obesity and metabolic disorders. Pregnant CD-1 mice were given ES from gestational day 6 to postnatal day 21 (short-term). After weaning, male pups of exposed dams were provided with a low-fat or a high-fat diet (LFD or HFD) and assessed after an additional 12 weeks. At the same time, one group of male pups continuously received ES (long-term). Treatment with low-dose ES, short or long-term, alleviated the development of
obesity and accumulation of hepatic
triglycerides induced by HFD. Analysis of gene expression, metabolic profile and gut microbiome indicates that ES treatment inhibits adipogenesis induced by HFD due to enhanced
lipid catabolism,
fatty acid oxidation and disturbance of gut microbiota composition. However, impaired
glucose and
insulin homeostasis were still conserved in HFD-fed mice exposed to ES. Furthermore, ES treatment
impaired glucose tolerance, affected hepatic gene expression,
fatty acids composition and serum metabolic profile, as well as disturbed gut microbiota in LFD-fed mice. In conclusion, ES treatment at levels close to the accepted daily intake during fetal development directly impact
glucose homeostasis, hepatic lipid metabolism, and gut microbiome dependent on the type of diet consumed. These findings provide a better understanding of the complex interactions of
environmental pollutants and diet at early life stages also in the context of
metabolic disease.