Effects of triphenyl phosphate exposure during fetal development on obesity and metabolic dysfunctions in adult mice: Impaired lipid metabolism and intestinal dysbiosis

Wang, Dezhen; Yan, Sen; Yan, Jin; Teng, Miaomiao; Meng, Zhiyuan; Li, Ruisheng; Zhou, Zhiqiang; Zhu, Wentao

doi:10.1016/j.envpol.2018.12.053

Cited by 85 publications

(39 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These modest changes in Agrp indicate an orexigenic neuropeptide profile in female mice, although we did not observe any distinct effects on food intake or feeding behaviors in females exposed to OPFRs. No other maternal OPFR studies has characterized feeding behaviors in rodents, whether on LFD or HFD (Baldwin et al, 2017; Patisaul et al, 2013; Wang et al, 2018; Wang et al, 2019). In terms of other EDCs, a replacement compound for BPA, bisphenol S, also increased Agrp with no change in Pomc , Npy or Cart , in male mice (no females examined) (Rezg, Abot, Mornagui, Aydi, & Knauf, 2018).…”

Section: Discussionmentioning

confidence: 99%

Maternal organophosphate flame‐retardant exposure alters offspring feeding, locomotor and exploratory behaviors in a sexually‐dimorphic manner in mice

Walley

Krumm

Yasrebi

et al. 2020

J of Applied Toxicology

View full text Add to dashboard Cite

Increased usage of organophosphate flame retardants (OPFRs) has led to detectable levels in pregnant women and neonates, which is associated with negative neurological outcomes. Therefore, we investigated if maternal OPFR exposure altered adult offspring feeding, locomotor, and anxiety‐like behaviors on a low‐fat (LFD) or high‐fat diet (HFD). Wild‐type C57Bl/6J dams were orally dosed with vehicle (sesame oil) or an OPFR mixture (1 mg/kg combination each of tris(1,3‐dichloro‐2‐propyl)phosphate, triphenyl phosphate and tricresyl phosphate) from gestation day 7 to postnatal day 14. After weaning, pups were fed either a LFD or HFD until 19 weeks of age. Locomotor and anxiety‐like behaviors were evaluated with the open field test, elevated plus maze, and metabolic cages. Feeding behaviors and meal patterns were analyzed by a Biological Data Acquisition System. Anogenital distance was reduced in OPFR‐exposed male pups, but no effect was detected on adult body weight. We observed interactions of OPFR exposure and HFD consumption on locomotor and anxiety‐like behavior in males, suggesting an anxiogenic effect while reducing overall nighttime activity. We also observed an interaction of OPFR exposure and HFD on weekly food intake and feeding behaviors. OPFR‐exposed males consumed more total HFD than oil‐exposed males during the 72‐hour trial. However, when arcuate gene expression was analyzed, OPFR exposure induced Agrp expression in females, which would suggest greater orexigenic tone. Collectively, the implications of our study are that the behavioral effects of OPFR exposure are modulated by adult HFD consumption, which may influence the metabolic and neurological consequences of maternal OPFR exposure.

show abstract

Section: Discussionmentioning

confidence: 99%

Maternal organophosphate flame‐retardant exposure alters offspring feeding, locomotor and exploratory behaviors in a sexually‐dimorphic manner in mice

Walley

Krumm

Yasrebi

et al. 2020

J of Applied Toxicology

View full text Add to dashboard Cite

show abstract

“…Perhaps the strongest argument raised against the transmission of epigenetic marks such as DNA methylation is that genome-wide epigenetic reprogramming in mammalian germline cells should erase epimutations from the preceding T A B L E 1 List of known obesogens and potential obesogens with selected end-points and references. The reader should also consult references in previous review articles 46,121 Major use category 131,132 Triphenyl Phosphate + + Lipid accumulation; increased body-weight and fat mass in mice 134,135 FM-550 + + Lipid accumulation; weight gain 134,135,137,138 Pesticide Chlorpyrifos + Weight gain and hyperinsulinemia in rats 141,142 Quinoxyfen + Induce adipogenesis and adipogenic gene expression in 3T3-L1 cells 90 Forchlorfenuron + Induce adipogenesis and adipogenic gene expression in 3T3-L1 cells 90 Flusilazole + Induce adipogenesis and adipogenic gene expression in 3T3-L1 cells generation. 111,112 Some investigators report stable transgenerational changes in DNA methylation 110,114,115 ; others found that the same chemicals induced epimutations and alterations in gene expression in the F1 generation, but that these were not conserved in F2 prospermatogonia.…”

Section: Obesogens Can Be Heritablementioning

confidence: 99%

Transgenerational effects of obesogens

Lee

Blumberg

2019

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Obesity and associated disorders are now a global pandemic. The prevailing clinical model for obesity is overconsumption of calorie‐dense food and diminished physical activity (the calories in—calories out model). However, this explanation does not account for numerous recent research findings demonstrating that a variety of environmental factors can be superimposed on diet and exercise to influence the development of obesity. The environmental obesogen model proposes that exposure to chemical obesogens during in utero and/or early life can strongly influence later predisposition to obesity. Obesogens are chemicals that inappropriately stimulate adipogenesis and fat storage, in vivo either directly or indirectly. Numerous obesogens have been identified in recent years and some of these elicit transgenerational effects on obesity as well as a variety of health end‐points after exposure of pregnant F0 females. Prenatal exposure to environmental obesogens can produce lasting effects on the exposed animals and their offspring to at least the F4 generation. Recent results show that some of these transgenerational effects of obesogen exposure can be carried across the generations via alterations in chromatin structure and accessibility. That some chemicals can have permanent effects on the offspring of exposed animals suggests increased caution in the debate about whether and to what extent exposure to endocrine‐disrupting chemicals and obesogens should be regulated.

show abstract

“…2017). In addition to adipogenesis, obesity has been also observed after in utero and lactational exposure to TPHP and was reported to result from modulation of the gut microbiome composition of mice (Wang et al. 2019).…”

Section: Discussionmentioning

confidence: 99%

Screening of House Dust from Chinese Homes for Chemicals with Liver X Receptors Binding Activities and Characterization of Atherosclerotic Activity Using an in Vitro Macrophage Cell Line and ApoE−/− Mice

Jia

Kang

et al. 2019

Environ Health Perspect

View full text Add to dashboard Cite

Background:Atherosclerotic cardiovascular disease has become the leading cause of death worldwide, and environmental pollutants are increasingly recognized as risk factors for atherosclerosis. Liver X receptors (LXRs) play a central role in atherosclerosis; however, LXR activity of organic pollutants and associated potential risk of atherosclerosis have not yet been characterized.Objectives:This study aimed to explore whether LXR-antagonistic chemicals are present in indoor house dust and, if so, to characterize this activity in relation to changes in macrophages in vitro and cardiovascular disease indicators in vivo in an atherosclerosis ApoE−/− mouse model.Methods:We used a His-LXRα-pull-down assay and a nontarget high-resolution mass spectrometry method to screen house dust collected from Chinese homes for LXRα- and LXRβ-antagonist activity. A chemical identified in this manner was assessed for its ability to induce cholesterol efflux and foam cell formation in RAW264.7 macrophages, to down-regulate the expression of two LXR-dependent genes, ABCA1 and ABCG1, and finally to induce atherosclerotic lesions in vivo using an ApoE−/− mouse model.Results:We identified the flame retardants triphenyl phosphate (TPHP) and 2-ethylhexyl diphenyl phosphate (EHDPP) in house dust samples and demonstrated their ability to antagonize LXRs. The potency of TPHP was similar to that of the LXR-antagonist SR9238. TPHP could also inhibit cholesterol efflux and promote foam cell formation in RAW264.7 macrophages and mouse peritoneal macrophages and significantly promoted atherosclerotic lesion formation in the ApoE−/− mouse model.Conclusions:We found LXR-antagonist chemicals in environmental samples of indoor dust from Chinese homes. One of the chemicals, TPHP, was able to promote the development of atherosclerotic lesions in the ApoE−/− mouse model. These results highlight the need to assess the LXR-antagonist activities of pollutants in future environmental management programs. https://doi.org/10.1289/EHP5039

show abstract

Effects of triphenyl phosphate exposure during fetal development on obesity and metabolic dysfunctions in adult mice: Impaired lipid metabolism and intestinal dysbiosis

Cited by 85 publications

References 46 publications

Maternal organophosphate flame‐retardant exposure alters offspring feeding, locomotor and exploratory behaviors in a sexually‐dimorphic manner in mice

Maternal organophosphate flame‐retardant exposure alters offspring feeding, locomotor and exploratory behaviors in a sexually‐dimorphic manner in mice

Transgenerational effects of obesogens

Screening of House Dust from Chinese Homes for Chemicals with Liver X Receptors Binding Activities and Characterization of Atherosclerotic Activity Using an in Vitro Macrophage Cell Line and ApoE−/− Mice

Contact Info

Product

Resources

About