In utero exposure to decabromodiphenyl ethane causes rapid growth in mice cubs by activating glycogenolysis and lipid synthesis

Decabromodiphenyl ethane (DBDPE) as a novel brominated flame retardant is frequently detected in environmental media due to its widespread use. Studies have shown that exposure to environmental pollutants in utero could lead to weight loss in newborns and obesity in adulthood. However, the mechanisms of how the cubs grow rapidly from low birth weight to obesity remain unclear. Although it has been reported that perinatal DBDPE exposure caused obesity in the offspring of mice in adulthood, its metabolic changes in offspring juvenile are unknown. Here, we monitored changes of body weight in cubs following exposure to DBDPE in utero. Furthermore, 1H NMR-based metabolomics was used to investigate the effects of in utero DBDPE exposure on the metabolic profile of neonates included days 1 and 25. Additionally, the expression levels of key genes in the relevant pathways were quantified. The results showed that exposure to high levels of DBDPE in utero caused cubs to be smaller at birth and grow rapidly during lactation. Metabolomics analysis showed that cubs in the exposed group consistently accelerated glycogenolysis and lipid synthesis to promote appetite and energy absorption, and achieved rapid growth in the subsequent lactation, which was further evidenced by the expression levels of genes related to glycolipid metabolism. These results reveal the mechanism for the first time how the weight loss of newborns in utero environmental pollutant exposure transformed into obesity in adulthood, although the exposures here were much higher than would be anticipated from the environment.