Prenatal low-dose DEHP exposure induces metabolic adaptation and obesity: Role of hepatic thiamine metabolism
[Display omitted] •We studied the effect of low-dose DEHP exposure on metabolic syndrome in offspring.•Prenatal low-dose DEHP exposure results in male offspring metabolic syndrome and gut microbiome dysbiosis.•Low-dose DEHP exposure reprograms hepatic thiamine transporters disrupting glucose metabol...
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Veröffentlicht in: | Journal of hazardous materials 2020-03, Vol.385, p.121534-121534, Article 121534 |
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Sprache: | eng |
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•We studied the effect of low-dose DEHP exposure on metabolic syndrome in offspring.•Prenatal low-dose DEHP exposure results in male offspring metabolic syndrome and gut microbiome dysbiosis.•Low-dose DEHP exposure reprograms hepatic thiamine transporters disrupting glucose metabolism.•Thiamine ameliorates DEHP-induced adipogenesis and insulin resistance.
Di-(2-ethylhexyl)-phthalate (DEHP) is a ubiquitous environmental pollutant and is widely used in industrial plastics. However, the long-term health implications of prenatal exposure to DEHP remains unclear. We set out to determine whether prenatal DEHP exposure can induce metabolic syndrome in offspring and investigate the underlying mechanisms. A mouse model of prenatal DEHP exposure (0.2, 2, and 20 mg/kg/day) was established to evaluate the long-term metabolic disturbance in offspring. The mice were profiled for the hepatic metabolome, transcriptome and gut microbiota to determine the underlying mechanisms. Thiamine supplementation (50 mg/kg/day) was administered to offspring to investigate the role of thiamine in ameliorating metabolic syndrome. Prenatal exposure to low-dose DEHP (0.2 mg/kg/day) resulted in metabolic syndrome, including abnormal adipogenesis, energy expenditure and glucose metabolism, along with dysbiosis of the gut microbiome, in male offspring. Notably, hepatic thiamine metabolism was disrupted in these offspring due to the dysregulation of thiamine transport enzymes, which caused abnormal glucose metabolism. Prenatal low-dose DEHP exposure caused life-long metabolic consequences in a sex-dependent manner, and these consequences were be attenuated by thiamine supplementation in offspring. Our findings suggest low-dose DEHP exposure during early life stages is a potential risk factor for later obesity and metabolic syndrome. |
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ISSN: | 0304-3894 1873-3336 |
DOI: | 10.1016/j.jhazmat.2019.121534 |