Association of polybrominated diphenyl ethers in two fat compartments with increased risk of insulin resistance in obese individuals

Helaleh, Murad I.H.; Diboun, Ilhame; Al-Tamimi, Nada; Al-Sulaiti, Haya; Al-Emadi, Mohamed; Madani, Aisha; Mazloum, Nayef; Latiff, Aishah A.; Elrayess, Mohamed A.

doi:10.1016/j.chemosphere.2018.06.108

Cited by 36 publications

(35 citation statements)

References 37 publications

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“…These were the same primary congeners reported in the DE-71 lot used in this study. Similar results on predominant congeners (BDE-47, -99, -100 and -153) have been found in women sampled recently 12,34,36,81,83 . The fast elimination of BDE-47 from livers of mice 43,84 it lacks unsubstituted carbons resulting in poor metabolism by the body and allowing for quick absorption and tissue retention, especially in liver 43,85 .…”

Section: Discussionsupporting

confidence: 84%

“…Studies have shown that levels of insulin, glucagon and glucagon-like peptide 1 (GLP-1) are altered in T2D leading to pathological glucose dyshomeostasis 57 36 . Animal studies have failed to show changes in insulin levels with adult exposure to BDE-47 29 or postnatal exposure to BDE-47 31 or perinatal exposure to a mixture of BFRs, including PBDEs and HBCDD 52 .…”

Section: Discussionmentioning

confidence: 99%

“…It is likely that congeners found in F1 liver, BDE-153 and BDE-28, contribute significantly to the pronounced diabetic phenotype seen in DE-71-exposed F1. Adverse diabetogenic symptoms have been associated with both of these PBDE congeners in human serum, breastmilk and children 34,35,36 . BDE-153 is positively associated with diabetes and/or MetS in studies of men and women in China 29,34 , in US 35 and with fasting hyperglycemia in Canada 33 but not in other populations 88,89,90 .…”

Section: Discussionmentioning

confidence: 99%

“…In particular, Lim and colleagues 35 reported that the positive association showed an inverted U-shape indicating a significant effect only at low and moderate PBDE exposure which supports the dose-dependent hormesis seen in our study. Moreover, BDE-28 may contribute to insulin-resistant diabetes typical of T2D 36 . Gestational diabetes mellitus (GDM) in healthy US pregnant women sampled from 2013-2015 is also positively associated with high body burdens of BDE-153 and BDE-28 37,38 .…”

Section: Discussionmentioning

confidence: 99%

“…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 . Additionally, exposure to BDE-28, -47, -99, -153, -154 and -183 increases the risk of gestational diabetes mellitus (GDM) in healthy US women 37,38,39 , a physiologically demanding condition that may increase the risk of MetS in adult offspring 40 .…”

Section: Introductionmentioning

confidence: 99%

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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

Kozlova

Chinthirla

Perez

et al. 2020

Preprint

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Polybrominated diphenyl ethers (PBDEs) are brominated flame retardant chemicals and environmental contaminants with endocrine-disrupting properties that are associated with diabetes and metabolic syndrome in humans. However, their diabetogenic actions are not completely characterized or understood. In this study, we investigated the effects of DE-71, a commercial penta-mixture of PBDEs, on glucose regulatory parameters in a perinatal exposure model using female C57Bl/6 mice. Results from in vivo glucose and insulin tolerance tests and ex vivo analyses showed that DE-71 produced fasting hyperglycemia, glucose intolerance, reduced sensitivity and delayed glucose clearance after insulin challenge, and exaggerated hepatic endocannabinoid tone in F1 offspring exposed to 0.1 mg/kg DE-71 relative to control. DE-71 effects on F0 dams were more limited indicating that indirect exposure to developing offspring is more detrimental. Other ex vivo glycemic correlates occur more generally in exposed F0 and F1, i.e., reduced plasma insulin and altered glucoregulatory endocrines, exaggerated sympathoadrenal activity, decreased thermogenic brown adipose tissue mass and reduced hepatic glutamate dehydrogenase enzymatic activity. Hepatic PBDE congener analysis indicated maternal transfer of BDE-28 and −153 to F1 at a collective level of 200 ng/g lipid, in range with maximum values detected in serum of human females. Given the persistent diabetogenic phenotype, especially pronounced in female offspring after developmental exposure to environmentally relevant levels of DE-71, additional animal studies should be conducted that further characterize PBDE-induced diabetic pathophysiology and identify critical developmental time windows of susceptibility. Longitudinal human studies should also be conducted to determine the risk of long-lasting metabolic consequences after maternal transfer of PBDEs during early-life development.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Kozlova

Chinthirla

Perez

et al. 2020

Preprint

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The Role of Environmental Disruptor Chemicals in the Development of Non Communicable Disease

Zarean

Poursafa

2019

Advances in Experimental Medicine and Biology

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Maternal probiotic supplementation protects against PBDE-induced developmental, behavior and metabolic reprogramming in a sexually dimorphic manner: Role of gut microbiome

Denys,

Kozlova,

Liu

et al. 2024

Arch Toxicol

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Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting persistent organic pollutants (POPs) used as flame retardants in a wide range of commercial applications. We have previously reported neurobehavioral and metabolic reprogramming produced by developmental PBDEs. PBDEs perturb the microbiome, an influencer of life-long health, while probiotic supplementation with Limosilactobacillus reuteri (LR) can avert neurobehavioral and endocrine disruption. We, therefore, tested the hypothesis that perinatal maternal LR supplementation would protect gut microbiome richness and diversity, developmental milestones, adult neurobehavior and metabolic homeostasis in PBDE-exposed offspring. C57BL/6N dams were orally exposed to a commercial penta-mixture of PBDEs, DE-71, at 0.1 mg/kg/day, or corn oil vehicle (VEH/CON) during gestation and lactation. Mice offspring received DE-71 or VEH/CON with or without co-administration of LR (ATCC-PTA-6475) indirectly via their mother from gestational day (GD) 0 until postnatal day (P)21 (Cohort 1), or continued to receive LR directly from P22 through adulthood (Cohort 2). Results of fecal 16S rRNA sequencing indicated age- and sex-dependent effects of DE-71 on gut microbial communities. Maternal LR treatment protected against DE-71-induced reduction in α-diversity in P22 females and against β-diversity alterations in P30 males. In females, DE-71 changed the relative abundance of specific bacterial taxa, such as Tenericutes and Cyanobacteria (elevated) and Deferribacterota (reduced). In males, several Firmicutes taxa were elevated, while Proteobacteria, Chlamydiae, and several Bacteroidota taxa were reduced. The number of disrupted taxa normalized by maternal LR supplementation was as follows: 100% in P22 females and 33% in males at P22 and 25% at P30. Maternal LR treatment protected against DE-71-induced delay of postnatal body weight gain in males and ameliorated the abnormal timing of incisor eruption in both sexes. Further, DE-71 produced exaggerated digging in both sexes as well as locomotor hyperactivity in females, effects that were mitigated by maternal LR only in females. Other benefits of LR therapy included normalization of glucose tolerance, insulin-to-glucose ratio and plasma leptin in adult DE-71 females (Cohort 2). This study provides evidence that probiotic supplementation can mitigate POP-induced reprogramming of neurodevelopment, adult neurobehavior, and glucose metabolism in association with modified gut microbial community structure in a sex-dependent manner.

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Association of polybrominated diphenyl ethers in two fat compartments with increased risk of insulin resistance in obese individuals

Cited by 36 publications

References 37 publications

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

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

The Role of Environmental Disruptor Chemicals in the Development of Non Communicable Disease

Maternal probiotic supplementation protects against PBDE-induced developmental, behavior and metabolic reprogramming in a sexually dimorphic manner: Role of gut microbiome

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