Journal
JOURNAL OF HAZARDOUS MATERIALS
Volume 385, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jhazmat.2019.121534
Keywords
DEHP; Prenatal exposure; Gut microbiota; Thiamine; Obesity
Categories
Funding
- National Natural Science Foundation of China [81671461, 81330067, 81872650]
- Natural Science Foundation of Jiangsu Province of China [BK20181366]
- Key Natural Science Foundation of the Jiangsu Higher Education Institutions of China [18KJA320003]
- Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine)
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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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