Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis

Strakovsky, Rita S.; Wang, Huan; Engeseth, Nicki J.; Flaws, Jodi A.; Helferich, William G.; Pan, Yuan Xiang; Lezmi, Stéphane

doi:10.1016/j.taap.2015.02.021

Cited by 141 publications

(111 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, treatment of adipocytes with TCDD, PCBs, DDT, BFRs, BPA, and PAHs impaired glucose uptake. Exposure of animals to PCBs (38), phthalates (142) (374), BFRs (431), or mixtures of POPs (336) impaired insulin sensitivity. Mechanisms for these effects are not fully understood, but may include reduced AT levels of Glut-4 mRNA or increased expression of inflammatory markers (both AT and circulating levels) associated with impaired glucose uptake or insulin resistance.…”

Section: Effects Of Pops On At Functionmentioning

confidence: 99%

Adipose Tissue as a Site of Toxin Accumulation

Jackson

Shoemaker

Larian

et al. 2017

Comprehensive Physiology

136

View full text Add to dashboard Cite

We examine the role of adipose tissue, typically considered an energy storage site, as a potential site of toxicant accumulation. Although the production of most persistent organic pollutants (POPs) was banned years ago, these toxicants persist in the environment due to their resistance to biodegradation and widespread distribution in various environmental forms (e.g., vapor, sediment, water). As a result, human exposure to these toxicants is inevitable. Largely due to their lipophilicity, POPs bioaccumulate in adipose tissue, resulting in greater body burdens of these environmental toxicants with obesity. POPs of major concern include polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and furans (PCDDs/PCDFs), and polybrominated biphenyls and diphenyl ethers (PBBs/PBDEs), among other organic compounds. In this review, we 1) highlight the physical characteristics of toxicants that enable them to partition into and remain stored in adipose tissue, 2) discuss the specific mechanisms of action by which these toxicants act to influence adipocyte function, and 3) review associations between POP exposures and the development of obesity and diabetes. An area of controversy relates to the relative potential beneficial versus hazardous health effects of toxicant sequestration in adipose tissue.

show abstract

Section: Effects Of Pops On At Functionmentioning

confidence: 99%

Adipose Tissue as a Site of Toxin Accumulation

Jackson

Shoemaker

Larian

et al. 2017

Comprehensive Physiology

136

View full text Add to dashboard Cite

show abstract

“…Epigenetic analysis of the CPT1A gene, the key ␤-oxidation enzyme, showed increased DNA methylation and altered H3K4me2, H3K36me3, H3Ac, and H4Ac in its transcription start site, revealing a novel regulatory mechanism for the transcription of CPT1A after BPA exposure. This study shows that both DNA methylation and histone modifications play an important role in EDC toxicity by influencing chromatin conformation and subsequent binding of transcription factors (44).…”

Section: Obesogenic Edc Exposure and Epigenetic Effectsmentioning

confidence: 78%

“…It is also clear that the complex interplay of DNA methylation, histone modifications, and noncoding RNA has not been studied yet in the context of obesogenic EDCs, because most studies in this young field have focused on DNA methylation. The study of Strakovsky et al (44) provides an elegant "proof of principle" that a combination of changes in histone marks and DNA methylation to key genes involved in mitochondrial metabolism underlie the effects of perinatal BPA exposure and latent onset of steatosis. More studies of this type are needed to better understand chromatin conformational changes by EDCs.…”

Section: Discussionmentioning

confidence: 99%

“…BPA induces the differentiation of 3T3-L1 mice preadipocytes in vitro at low nanomolar concentrations (43), which has been associated with increased global DNA methylation at higher concentrations (34). In an elegant study that is one of the first to combine analysis of DNA methylation and histone modifications after EDC exposure, Strakovsky et al (44) show that early life BPA exposure increased fat/lean mass and exacerbated high-fat diet induced hepatic steatosis in adult males only. On a molecular level, BPA exposure was associated with decreased expression of genes in males early in life that are involved in triglyceride synthesis and mitochondrial ␤-oxidation.…”

Section: Obesogenic Edc Exposure and Epigenetic Effectsmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals

Stel

Legler

2015

Endocrinology

View full text Add to dashboard Cite

Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans.

show abstract

“…. ) in rodents demonstrating gender-and dose-dependent effects (Miyawaki et al, 2007;Newbold et al, 2009;Strakovsky et al, 2015;Wei et al, 2011).…”

Section: Figmentioning

confidence: 99%

Obesogen effects after perinatal exposure of 4,4′-sulfonyldiphenol (Bisphenol S) in C57BL/6 mice

et al. 2016

View full text Add to dashboard Cite

Bisphenol A were removed from consumer products and replaced by chemical substitutes such as Bisphenol S (BPS). Based on their structural similarity, BPS may be obesogen like Bisphenol A in mice. Our objective was to determine the impact of BPS on lipid homeostasis in C57Bl/6 mice after perinatal and chronic exposure. Pregnant mice were exposed to BPS via the drinking water (0.2; 1.5; 50μg/kg bw/d). Treatment began at gestational day 0 and continued in offspring up to 23-weeks old. Then, offspring mice were fed with a standard or high fat diet. The body weight, food consumption, fat mass and energy expenditure were measured. A lipid load test was performed to check the postprandial triglyceridemia. Plasma parameters and mRNA gene expression in adipose tissues were also analysed. BPS induced overweight in male mice offspring fed with a HFD at the two highest doses. There was no change in food intake and energy expenditure. The overweight was correlated to the fat mass, hyperinsulinemia and hyperleptinemia. The plasma triglyceride clearance was significantly increased with BPS and tyloxapol(®) (triglyceride clearance inhibitor) reversed this phenomenon. BPS induced alteration in mRNA expression of marker genes involved in adipose tissue homeostasis: hormone sensitive lipase, PPARγ, insulin receptor, SOCS3 and adiponectin. This is the first time that BPS is described as obesogenic at low doses and after perinatal and chronic exposure in male mice. BPS potentiated the obesity induced by a HFD by inducing the lipid storage linked to faster lipid plasma clearance.

show abstract

Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis

Cited by 141 publications

References 50 publications

Adipose Tissue as a Site of Toxin Accumulation

Adipose Tissue as a Site of Toxin Accumulation

The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals

Obesogen effects after perinatal exposure of 4,4′-sulfonyldiphenol (Bisphenol S) in C57BL/6 mice

Contact Info

Product

Resources

About