In utero and lactational exposure to BDE-47 promotes obesity development in mouse offspring fed a high-fat diet: impaired lipid metabolism and intestinal dysbiosis
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In this study, we investigated the effects of in utero and lactational exposure to BDE-47 on the progression of obesity and metabolic dysfunction in a diet-induced obesity model. Pregnant ICR mice were treated via oral gavage with low doses of BDE-47 (0, 0.002, and 0.2 mg/kg body weight) from gestational day 6 to postnatal day 21. After weaning, male offspring were fed an AIN93-based normal diet (ND) or high-fat diet (HFD: 60% calories from fat) for 14 weeks. We examined body weight, liver weight, histopathology, blood biochemistry, gene expression, and serum metabolic changes. A combination of 16S rRNA gene sequencing and 1H NMR-based metabolomics was conducted to examine the effects of BDE-47 on the gut microbiome. Results showed that in utero and lactational exposure to BDE-47 caused a worsening of HFD-induced obesity, hepatic steatosis, and injury; impaired glucose homeostasis and metabolic dysfunction, and mRNA levels of genes involved in lipid metabolism were significantly altered in the BDE-47-treated HFD group. The gut microbiome were perturbed by BDE-47, causing diversity reduction, compositional alteration, and metabolic changes. These changes were more pronounced for BDE-47-treated HFD mice. All these results indicate that early life exposure to low doses of BDE-47 can promote obesity and the development of metabolic dysfunction.
KeywordsBDE-47 Obesity NAFLD Gut microbiome Metabolomics
We gratefully acknowledge the financial support from National Key Research and Development Program of China (2016YFD0200202), the National Natural Science Foundation of China (21337005); and the Young Elite Scientists Sponsorship Program by CAST.
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Conflict of interest
The authors report no conflicts of interest.
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