Bisphenol-A Impairs Insulin Action and Up-Regulates Inflammatory Pathways in Human Subcutaneous Adipocytes and 3T3-L1 Cells

Valentino, Rossella; D’Esposito, Vittoria; Passaretti, Federica; Liotti, Antonietta; Cabaro, Serena; Longo, Michele; Perruolo, Giuseppe; Oriente, Francesco; Béguinot, Francesco; Formisano, Pietro

doi:10.1371/journal.pone.0082099

Cited by 107 publications

(89 citation statements)

References 56 publications

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“…3). In agreement with the recent finding that BPA up-regulates inflammatory pathways in 3T3-L1 cells and in adult human subcutaneous adipocytes (Valentino et al 2013), our data corroborated the hypothesis that the strong relationship between BPA and the inflammatory state of adipose depots that occur in late obesity and in metabolic syndrome can be induced during childhood.…”

Section: Discussionsupporting

confidence: 92%

“…A recent study (Valentino et al 2013) demonstrated a reduced insulin-stimulated tyrosine phosphorylation of insulin receptors in adult adipocytes treated with BPA and a consistent reduction of insulin downstream signaling. Another study reported that environmentally relevant BPA concentrations in adipocytes from children increase the expression and the enzymatic activity of 11b-hydroxysteroid dehydrogenase type 1.…”

Section: Introductionmentioning

confidence: 84%

“…Most of the published studies analyze the effects of BPA on adipogenesis in murine 3T3-L1 cells or in human cell cultures obtained from adult adipose tissue (Masuno et al 2005, Hugo et al 2008, Valentino et al 2013. A recent paper described the effects of BPA on adipogenesis using adipose cells from children as a model system .…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 84%

See 1 more Smart Citation

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

Menale¹,

Piccolo²,

Cirillo³

et al. 2015

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…They found that, after perinatal exposure to BPA, a reduction in adiponectin gene expression and production was observed in male offspring later in life and that at high BPA doses the metabolic dysfunction was detected at earlier age. Interestingly, a recent in vitro study using human adipocytes [53] revealed that low doses of BPA impair insulinstimulated glucose utilization and insulin signaling pathway thus dysregulating adipocytes function. Furthermore, Angle and collaborators [54], investigating the effects of fetal BPA exposure in male mice, found an increase in body weight and abdominal fat mass, corresponding to an increase in adipocyte number and size.…”

Section: Bpa Affects White Adipose Tissue Physiology and Its Endocrinmentioning

confidence: 99%

Adverse Effects of Bisphenol A Exposure on Glucose Metabolism Regulation

Menale¹,

Mita²,

Diano³

et al. 2016

TOBIOTJ

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Bisphenol A (BPA) is used as basic chemical compound in the production of polycarbonate food containers or epoxy resins coating metallic cans for food and beverages conservation. Its xeno-estrogenic activity alters endocrine-metabolic pathways modulating glucose metabolism and increasing the risk of developing diabetes, insulin resistance, and obesity. Based on in vitro and in vivo experimental research, here we report some of the major BPA adverse effects on tissues that play a key role in the regulation on the whole body's metabolism. Evidences have shown that BPA is able to exert its endocrine disrupting action altering glucose metabolism and contributing to the onset of metabolic disorders, acting on liver functions and affecting insulin production by the pancreas. Exposure to BPA has been reported also to modulate glucose utilization in muscles, as well as to interfere with adipose tissue endocrine function. In addition, to peripheral tissues, recent studies have shown that BPA by acting in the Central Nervous System affects neuroendocrine regulation of glucose metabolism, promoting glucose metabolism dysfunction such as glucose intolerance and insulin resistance. Thus, exposure to BPA seems to be an important risk factor in the onset of obesity and metabolic syndrome. However, its mechanisms of action need to be further investigated to provide a major evaluation of risk assessment.

show abstract

“…They found that, after perinatal exposure to BPA, a reduction in adiponectin gene expression and production was observed in male offspring later in life and that at high BPA doses the metabolic dysfunction was detected at earlier age. Interestingly, a recent in vitro study using human adipocytes [53] revealed that low doses of BPA impair insulin-stimulated glucose utilization and insulin signaling pathway thus dysregulating adipocytes function. Furthermore, Angle and collaborators [54], investigating the effects of fetal BPA exposure in male mice, found an increase in body weight and abdominal fat mass, corresponding to an increase in adipocyte number and size.…”

Section: Bpa Affects White Adipose Tissue Physiology and Its Endocrinmentioning

confidence: 99%

Adverse Effects of Bisphenol A Exposure on Glucose Metabolism Regulation

Menale¹,

Mita²,

Diano³

et al. 2015

TOBIOTJ

View full text Add to dashboard Cite

Bisphenol A (BPA) is used as basic chemical compound in the production of polycarbonate food containers or epoxy resins coating metallic cans for food and beverages conservation. Its xenoestrogenic activity alters endocrine-metabolic pathways modulating glucose metabolism and increasing the risk of developing diabetes, insulin resistance, and obesity. Based on in vitro and in vivo experimental research, here we report some of the major BPA adverse effects on tissues that play a key role in the regulation on the whole body's metabolism. Evidences have shown that BPA is able to exert its endocrine disrupting action altering glucose metabolism and contributing to the onset of metabolic disorders, acting on liver functions and affecting insulin production by the pancreas. Exposure to BPA has been reported also to modulate glucose utilization in muscles, as well as to interfere with adipose tissue endocrine function. In addition, to peripheral tissues, recent studies have shown that BPA by acting in the Central Nervous System affects neuroendocrine regulation of glucose metabolism, promoting glucose metabolism dysfunction such as glucose intolerance and insulin resistance. Thus, exposure to BPA seems to be an important risk factor in the onset of obesity and metabolic syndrome.However, its mechanisms of action need to be further investigated to provide a major evaluation of risk assessment.

show abstract

Bisphenol-A Impairs Insulin Action and Up-Regulates Inflammatory Pathways in Human Subcutaneous Adipocytes and 3T3-L1 Cells

Cited by 107 publications

References 56 publications

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

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

Adverse Effects of Bisphenol A Exposure on Glucose Metabolism Regulation

Adverse Effects of Bisphenol A Exposure on Glucose Metabolism Regulation

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