decabromodiphenyl-ethane and Obesity

Decabromodiphenyl ethane (DBDPE) is a major alternative to BDE-209 owing to its lower toxicity. However, the mass production and increased consumption of DBDPE in recent years have raised concerns related to its adverse health effects. However, the effect and mechanism of DBDPE on cardiotoxicity have rarely been studied. In the present study, we investigated the impacts of DBDPE on the cardiovascular system in male SD rats and then explored the underlying mechanisms to explain the cardiotoxicity of DBDPE using AC16 cells. Under in vivo conditions, male rats were administered with an oral dosage of DBDPE at 0, 5, 50, and 500 mg/kg/day for 28 days, respectively. Histopathological analysis demonstrated that DBDPE induced cardiomyocyte injury and fibrosis, and ultrastructural observation revealed that DBDPE could induce mitochondria damage and dissolution. DBDPE could thus decrease the level of MYH6 and increase the level of SERCA2, which are the two key proteins involved in the maintenance of homeostasis during myocardial contractile and diastolic processes. Furthermore, DBDPE could increase the serum levels of glucose and low-density lipoprotein but decrease the content of high-density lipoprotein. In addition, DBDPE could activate the PI3K/AKT/GLUT2 and PPARγ/RXRα signaling pathways in AC16 cells. In addition, DBDPE decreased the UCP2 level and ATP synthesis in mitochondria both under in vitro and in vivo conditions, consequently leading to apoptosis via the Cytochrome C/Caspase-9/Caspase-3 pathway. Bisulfite sequencing PCR (BSP) identified the hypermethylation status of fat mass and obesity-associated gene (FTO). 5-aza exerted the opposite effects on the PI3K/AKT/GLUT2, PPARγ/RXRα, and Cytochrome C/Caspase-9/Caspase-3 signaling pathways induced by DBDPE in AC16 cells. In addition, the DBDPE-treated altered levels of UCP2, ATP, and apoptosis were also found to be significantly reversed by 5-aza in AC16 cells. These results suggested that FTO hypermethylation played a regulative role in the pathological process of DBDPE-induced glycolipid metabolism disorder, thereby contributing to the dysfunction of myocardial contraction and relaxation through cardiomyocytes fibrosis and apoptosis via the mitochondrial-mediated apoptotic pathway resulting from mitochondrial dysfunction.

Topics: Adenosine Triphosphate; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Animals; Apoptosis; Bromobenzenes; Cardiotoxicity; Caspase 3; Caspase 9; Cytochromes c; Fibrosis; Heart Diseases; Male; Obesity; Phosphatidylinositol 3-Kinases; PPAR gamma; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley

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,

Topics: Animals; Bromobenzenes; Environmental Pollutants; Female; Flame Retardants; Glycogenolysis; Halogenated Diphenyl Ethers; Lipids; Mice; Obesity; Pregnancy; Weight Loss

Decabromodiphenyl Ethane (DBDPE), a kind of new brominated flame retardants (NBFRs) used to replace DecaBDE, has been frequently detected in the environment and human samples. In this study, we explored its toxic effects on male mouse offspring after perinatal exposure to DBDPE. During the perinatal period, pregnant ICR mice were exposed to DBDPE (100 μg/kg body weight) via oral gavage. After weaning, male offspring were fed on a low-fat diet and a high-fat diet, respectively. We measured and recorded body weight, liver weight, and epididymis fat mass, blood biochemical markers, metabolites changes in liver, and gene expression involved in lipid and glucose homeostasis. The results showed that perinatal exposure to DBDPE increased the risk of obesity in mouse offspring and affected triglyceride synthesis, bile secretion, purine synthesis, mitochondrial function and glucose metabolism, furthermore, the use of HFD feeding may further exacerbate these effects. All of these results show that early-life exposure to low doses of DBDPE can promote the development of metabolic dysfunction, which in turn induces obesity.

Topics: Animals; Bromobenzenes; Diet, High-Fat; Female; Flame Retardants; Homeostasis; Humans; Liver; Male; Mice; Mice, Inbred ICR; Obesity; Pregnancy; Risk