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

Abstract

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 H 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.

Developmental Exposure to 2,2′,4,4′-Tetrabromodiphenyl Ether Permanently Alters Blood-Liver Balance of Lipids in Male Mice

“…Fatty changes in liver were previously shown in juvenile mice exposed for 28 days to 0.45 mg/kg body weight of BDE-47 ( 73 ). Liver steatosis associated with increased expression of Cd36 was recently shown in mice exposed to low doses of BDE-47 perinatally and further kept on high fat diet for 14 weeks ( 74 ). Liver fatty degeneration was also demonstrated in adult rats exposed to high dose (2,000 mg/kg body weight) of pentaBDE ( 75 , 76 ) and in prepubertal rats exposed to high doses (300 and 600 mg/kg body weight) of decaBDE ( 77 ).…”

Maternal Transfer of Environmentally Relevant Polybrominated Diphenyl Ethers (PBDEs) Produces a Diabetic Phenotype and Disrupts Glucoregulatory Hormones and Hepatic Endocannabinoids in Adult Mouse Female Offspring

“…Alternatively, the relatively greater susceptibility of exposed F0 females in our study may be due to the combination of PBDE congeners present in DE-71. In adult male rats and mice BDE-47 treatment produces hyperglycemia in one study and diabetic symptoms in others but only when paired in two-hit models 30,31 . Interestingly, our results using DE-71 are similar to those produced by two brominated flame retardants not found in DE-71, BDE-209 (hyperglycemia with reduced insulin) 28 and Firemaster-550 (apparent glucose intolerance) 27 .…”

“…Seven days following IPGTT, an insulin tolerance test (ITT) was performed on mice fasted ON for 9h and then injected with Humulin R bolus (0.5 U/kg bw, i.p.). Tail blood was collected and glucose sampled at time 0 (FBG), 15,30,45,60,90 and 120 min post-injection. The area under (AUC) or above the glycemia curve (inverse AUC) was calculated over 0-120 min post injection.…”

“…Epidemiological studies suggest that the escalating production and environmental presence of a number of metabolic disrupting chemicals (MDC) over the past four decades may contribute to the pathogenesis of metabolic diseases 25 . Mounting evidence has implicated brominated POPs in the pathogenesis of T2D and metabolic syndrome (MetS) 26,27,28,29,30,31,32,33,34 . In particular, diabetes and/or MetS are positively associated with high body burdens of individual PBDE congeners including: BDE-28, -153, and -47, one of the most abundant PBDE congeners detected in the environment and in human tissues 29,34,35,36 .…”

Toxicity, Pharmacokinetics, and Gut Microbiome of Oral Administration of Sesterterpene MHO7 Derived from a Marine Fungus

“…However, in the isoproterenol-induced acute myocardial ischemia model, the amounts of Rikenellaceae RC9 gut group, Ruminococcus 1, and Bacteroidales S24-7 group were elevated while Ruminiclostridium 9, Lachnoclostridium, and Ruminococcaceae UCG-014 were reduced. The enrichments of Ruminiclostridium 5 and Rikenellaceae RC9 gut group were considered to be related to the lipid metabolism [34,35]. Furthermore, genus Ruminiclostridium 9 was positive to blood IgM level and colitis histological scores [36] and Anaeroplasma was supposed to be a potential anti-inflammatory probiotic for the treatment of chronic intestinal inflammation [37].…”