Perinatal Exposure to Bisphenol A at Reference Dose Predisposes Offspring to Metabolic Syndrome in Adult Rats on a High-Fat Diet

Jie, Wei; Lin, Yi; Li, Yuanyuan; Ying, Chenjiang; Chen, Jun; Song, Lihua; Zhao, Zhou; Lv, Ziquan; Xia, Wei; Chen, Xi; Xu, Shunqing

doi:10.1210/en.2011-0045

Cited by 264 publications

(227 citation statements)

References 49 publications

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“…In the present study, we first demonstrated that long-term oral exposure to BPA induced glucose intolerance after the neonatal period by increasing insulin resistance in a manner that was not related to b cell dysfunction. These findings are consistent with previously published epidemiologic data (Lang et al 2008, Shankar & Teppala 2011, Wang et al 2012 and animal studies (Alonso-Magdalena et al 2006, Wei et al 2011, Batista et al 2012). In two large epidemiologic studies, urinary BPA level was positively associated with type 2 diabetes mellitus (Shankar & Teppala 2011) and with obesity and insulin resistance (Wang et al 2012).…”

Section: Discussionsupporting

confidence: 93%

Long-term oral exposure to bisphenol A induces glucose intolerance and insulin resistance

Moon¹,

Jeong²,

Oh³

et al. 2015

Journal of Endocrinology

105

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Bisphenol A (BPA) is a widely used endocrine disruptor. Recent epidemiologic results have suggested an association between exposure to BPA and cardiovascular disease, type 2 diabetes, and obesity. We investigated the in vivo effects of long-term oral exposure to BPA on insulin resistance and glucose intolerance. In the present study, 4-to 6-week-old male mice on a high-fat diet (HFD) were treated with 50 mg/kg body weight per day of BPA orally for 12 weeks. Long-term oral exposure to BPA along with an HFD for 12 weeks induced glucose intolerance in growing male mice. Intraperitoneal glucose tolerance tests showed that the mice that received an HFD and BPA exhibited a significantly larger area under the curve than did those that received an HFD only (119.9G16.8 vs 97.9G18.2 mM/min, PZ0.027). Body weight, percentage of white adipose tissue, and percentage of body fat did not differ between the two groups of mice. However, treatment with BPA reduced Akt phosphorylation at position Thr308 and GSK3b phosphorylation at position Ser9 in skeletal muscle. BPA tended to decrease serum adiponectin levels and to increase serum interleukin 6 and tumor necrosis factor a, although these findings were not statistically significant. Treatment with BPA did not induce any detrimental changes in the islet area or morphology or the insulin content of b cells. In conclusion, long-term oral exposure to BPA induced glucose intolerance and insulin resistance in growing mice. Decreased Akt phosphorylation in skeletal muscle by way of altered serum adipocytokine levels might be one mechanism by which BPA induces glucose intolerance.

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Section: Discussionsupporting

confidence: 93%

Long-term oral exposure to bisphenol A induces glucose intolerance and insulin resistance

Moon¹,

Jeong²,

Oh³

et al. 2015

Journal of Endocrinology

105

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“…In the past decades, EDCs have been recognized to exhibit a lack of linear dose-dependent relationship with endocrine abnormalities, showing instead inverted U-shaped curves (Alonso-Magdalena et al 2011). In a recent report from Wei et al (2011), perinatal exposure to BPA (50 mg/kg per day) induces hyperinsulinemia and impaired glucose regulation in SD rat offspring. Interestingly, the effects are not observed at higher doses.…”

Section: Discussionmentioning

confidence: 99%

Low-level phenolic estrogen pollutants impair islet morphology and β-cell function in isolated rat islets

Song¹,

Xia²,

Zhao³

et al. 2012

Journal of Endocrinology

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Phenolic estrogen pollutants, a class of typical endocrinedisrupting chemicals, have attracted public attention due to their estrogenic activities of imitating steroid hormone 17b-estradiol (E 2 ) effects. Exposure to these pollutants may disrupt insulin secretion and be a risk factor for type 2 diabetes. In this study, we investigated the direct effects of phenolic estrogen diethylstilbestrol (DES), octylphenol (OP), nonylphenol (NP), and bisphenol A (BPA) on rat pancreatic islets in vitro, whose estrogenic activities were DESONPOOPOBPA. Isolated b-cells were exposed to E 2 , DES, OP, NP, or BPA (0, 0 . 1, 0 . 5, 2 . 5, 25, and 250 mg/l) for 24 h. Parameters of insulin secretion, content, and morphology of b-cells were measured. In the glucose-stimulated insulin secretion test, E 2 and DES increased insulin secretion in a dose-dependent manner in a 16 . 7 mM glucose condition. However, for BPA, NP, or OP with lower estrogenic activity, the relationship between the doses and insulin secretion was an inverted U-shape. Moreover, OP, NP, or BPA (25 mg/l) impaired mitochondrial function in b-cells and induced remarkable swelling of mitochondria with loss of distinct cristae structure within the membrane, which was accompanied by disruption of mRNA expression of genes playing a key role in b-cell function (Glut2 (Slc2a2), Gck, Pdx1, Hnf1a, Rab27a, and Snap25), and mitochondrial function (Ucp2 and Ogdh). Therefore, these phenolic estrogens can disrupt islet morphology and b-cell function, and mitochondrial dysfunction is suggested to play an important role in the impairment of b-cell function.

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“…Previous studies in rodents indicated that BPA directly affects pancreatic b-cell functions (Alonso-Magdalena et al 2010, Wei et al 2011), and a recent paper has demonstrated in a rat insulinoma cell line that BPA affects pancreatic function on insulin production by decreasing insulin production and secretion (Lin et al 2013).…”

Section: Bpa Regulates Insulin Productionmentioning

confidence: 97%

Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders

Menale¹,

Piccolo²,

Cirillo³

et al. 2015

Journal of Molecular Endocrinology

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Bisphenol A (BPA) is a xenobiotic endocrine-disrupting chemical. In vitro and in vivo studies have indicated that BPA alters endocrine-metabolic pathways in adipose tissue, which increases the risk of metabolic disorders and obesity. BPA can affect adipose tissue and increase fat cell numbers or sizes by regulating the expression of the genes that are directly involved in metabolic homeostasis and obesity. Several studies performed in animal models have accounted for an obesogen role of BPA, but its effects on human adipocytesespecially in children -have been poorly investigated. The aim of this study is to understand the molecular mechanisms by which environmentally relevant doses of BPA can interfere with the canonical endocrine function that regulates metabolism in mature human adipocytes from prepubertal, non-obese children. BPA can act as an estrogen agonist or antagonist depending on the physiological context. To identify the molecular signatures associated with metabolism, transcriptional modifications of mature adipocytes from prepubertal children exposed to estrogen were evaluated by means of microarray analysis. The analysis of deregulated genes associated with metabolic disorders allowed us to identify a small group of genes that are expressed in an opposite manner from that of adipocytes treated with BPA. In particular, we found that BPA increases the expression of pro-inflammatory cytokines and the expression of FABP4 and CD36, two genes involved in lipid metabolism. In addition, BPA decreases the expression of PCSK1, a gene involved in insulin production. These results indicate that exposure to BPA may be an important risk factor for developing metabolic disorders that are involved in childhood metabolism dysregulation.

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Perinatal Exposure to Bisphenol A at Reference Dose Predisposes Offspring to Metabolic Syndrome in Adult Rats on a High-Fat Diet

Cited by 264 publications

References 49 publications

Long-term oral exposure to bisphenol A induces glucose intolerance and insulin resistance

Long-term oral exposure to bisphenol A induces glucose intolerance and insulin resistance

Low-level phenolic estrogen pollutants impair islet morphology and β-cell function in isolated rat islets

Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders

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