Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator-activated receptor gamma-independent mechanism
| العنوان: | Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator-activated receptor gamma-independent mechanism |
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| المؤلفون: | Amanda Janesick, Connie Chow, Xia Li, Stephanie C. Casey, Raquel Chamorro-Garcia, Bruce Blumberg, Séverine Kirchner |
| المصدر: | Chamorro-García, R; Kirchner, S; Li, X; Janesick, A; Casey, SC; Chow, C; et al.(2012). Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator-activated receptor gamma-independent mechanism. Environmental Health Perspectives, 120(7), 984-989. doi: 10.1289/ehp.1205063. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/5637j5bc Chamorro-Garcia, Raquel; Kirchner, Séverine; Li, Xia; Janesick, Amanda; Casey, Stephanie C; Chow, Connie; et al.(2012). Bisphenol A Diglycidyl Ether Induces Adipogenic Differentiation of Multipotent Stromal Stem Cells through a Peroxisome Proliferator-Activated Receptor Gamma-Independent Mechanism. Environmental Health Perspectives, 120(7), 984-989. doi: 10.1289/ehp.1205063. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/5mc2378v Environmental Health Perspectives |
| بيانات النشر: | eScholarship, University of California, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | obesity, PPARγ, Health, Toxicology and Mutagenesis, Peroxisome proliferator-activated receptor, Adipose tissue, Estrogen receptor, MSCs, 010501 environmental sciences, Polymerase Chain Reaction, 01 natural sciences, adipose-tissue, Mice, chemistry.chemical_compound, Adipocyte, Medicine and Health Sciences, Bisphenol A diglycidyl ether, ppar-gamma, Cells, Cultured, adipocyte differentiation, chemistry.chemical_classification, 0303 health sciences, Adipogenesis, Life Sciences, Cell Differentiation, endocrine disruption, Flow Cytometry, BPA, 3. Good health, Endocrine disruptor, BADGE, medicine.medical_specialty, endocrine system, Biology, in-vitro, perinatal exposure, metabolic syndrome, adipogenesis, 03 medical and health sciences, obesogen, 3T3-L1 Cells, Internal medicine, medicine, Animals, Humans, Benzhydryl Compounds, 030304 developmental biology, 0105 earth and related environmental sciences, Research, Multipotent Stem Cells, Public Health, Environmental and Occupational Health, PPAR gamma endocrine-disrupting chemicals, environmental chemicals, canned foods, PPAR gamma, Endocrinology, chemistry, 13. Climate action, Epoxy Compounds, Obesogen |
| الوصف: | Research Bisphenol A Diglycidyl Ether Induces Adipogenic Differentiation of Multipotent Stromal Stem Cells through a Peroxisome Proliferator–Activated Receptor Gamma-Independent Mechanism Raquel Chamorro-Garcia, 1, * Severine Kirchner, 1, * Xia Li, 1 Amanda Janesick, 1 Stephanie C. Casey, 1 Connie Chow, 1 and Bruce Blumberg 1,2 1 Department of Developmental and Cell Biology, and 2 Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, California, USA B ackground : Bisphenol A (BPA) and bisphenol A diglycidyl ether (BADGE), used in manufacturing coatings and resins, leach from packaging materials into food. Numerous studies suggested that BPA and BADGE may have adverse effects on human health, including the possibil- ity that exposure to such chemicals can be superimposed on traditional risk factors to initiate or exacerbate the development of obesity. BPA is a suspected obesogen, whereas BADGE, described as a peroxisome proliferator–activated receptor gamma (PPARγ) antagonist, could reduce weight gain. O bjectives : We sought to test the adipogenic effects of BADGE in a biologically relevant cell culture model. M ethods : We used multipotent mesenchymal stromal stem cells (MSCs) to study the adipogenic capacity of BADGE and BPA and evaluated their effects on adipogenesis, osteogenesis, gene expres- sion, and nuclear receptor activation. D iscussion : BADGE induced adipogenesis in human and mouse MSCs, as well as in mouse 3T3-L1 preadipocytes. In contrast, BPA failed to promote adipogenesis in MSCs, but induced adipogenesis in 3T3-L1 cells. BADGE exposure elicited an adipogenic gene expression profile, and its ability to induce adipogenesis and the expression of adipogenic genes was not blocked by known PPARγ antagonists. Neither BADGE nor BPA activated or antagonized retinoid “X” receptor (RXR) or PPARγ in transient transfection assays. C onclusions : BADGE can induce adipogenic differentiation in both MSCs and in preadipocytes at low nanomolar concentrations comparable to those that have been observed in limited human bio monitoring. BADGE probably acts through a mechanism that is downstream of, or parallel to, PPARγ. K ey words : adipogenesis, BADGE, BPA, endocrine disruption, MSCs, obesogen, PPARγ. Environ Health Perspect 120:984–989 (2012). http://dx.doi.org/10.1289/ehp.1205063 [Online 25 May Bisphenol A (BPA) is used in the synthesis of polycarbonate plastics, epoxy adhesives, and the lining of food containers. Bisphenol A diglycidyl ether (BADGE) is a synthesis prod- uct of BPA and epichlorhydrin used in the manufacture of epoxy resins, paints, and as a coating on food containers. BPA and BADGE are present in many commonly used prod- ucts including beverage containers, baby bottles, and dental composites. Both migrate from containers into foods, and are routinely ingested (Cabado et al. 2008; Cao et al. 2009). Studies of BADGE metabolism suggest that it is not a significant source of BPA (Climie et al. 1981) although BPA leaches from some BADGE-containing dental sealants (Joskow et al. 2006; Olea et al. 1996). BPA is an environmental endocrine- disrupting chemical (EDC) found in 95% of human urine samples (Calafat et al. 2008) as well as in serum, breast milk, and fat (reviewed by Rubin 2011; Taylor et al. 2011). Despite some controversy, the prevailing view in the scientific community is that BPA has impor- tant, deleterious effects in animals by acting on multiple target tissues (reviewed by Rubin 2011; Taylor et al. 2011), and BPA levels have been associated with adverse health outcomes in humans (Lang et al. 2008). Estrogenic and antiandrogenic effects of BADGE have been reported (Olea et al. 1996; Satoh et al. 2004); however, the manufacturers of BADGE have disputed any endocrine- disrupting, oncogenic, or mutagenic effects (Poole et al. 2004). BADGE and its chloro hydroxy derivatives induced proliferation of human breast cancer cells but did not bind to the estrogen receptor (Nakazawa et al. 2002). BADGE exposure caused developmental tox- icity during gestation and lactation in rats (Hyoung et al. 2007) and toxicity in cell cul- ture (Ramilo et al. 2006). Overall, the pres- ence of BADGE in food cannot be considered a health benefit and may be a health risk. Obesity is caused by complex interactions among genetic, behavioral, and environmental factors, and EDC exposure is now thought to be a risk factor for obesity (reviewed by Janesick and Blumberg 2011; La Merrill and Birnbaum 2011; Tang-Peronard et al. 2011). Our “obesogen hypothesis” proposes a link between developmental EDC exposure and obesity. Obesogens are functionally defined as chemicals that promote obesity by increas- ing the number of fat cells (and fat storage into existing fat cells) by changing the amount of calories burned at rest, by altering energy balance to favor storage of calories, and by volume altering the mechanisms through which the body regulates appetite and satiety (reviewed by Janesick and Blumberg 2011). Most evidence suggests that BPA acts as an obesogen, in vitro and in vivo. BPA induced adipocyte differentiation and adipo- genic marker genes in 3T3-L1 preadipocytes (Masuno et al. 2005). Perinatal treatment of rats (Rubin et al. 2001; Somm et al. 2009) and mice (Miyawaki et al. 2007) with low doses of BPA led to increased fat mass (reviewed by Rubin 2011). Some studies suggested that different BPA dosing regimens might not increase body weight in rats (Nunez et al. 2001; Seidlova-Wuttke et al. 2005) or mice (Ryan et al. 2010), and thus further studies are needed to clarify exactly how BPA pro- motes adipogenesis and obesity. The obesogenic properties of BADGE are yet to be thoroughly investigated. BADGE was identified as an antagonist of peroxi- some proliferator–activated receptor gamma (PPARγ) [its IC 50 (the concentration of BADGE at which 50% inhibition of the response is observed) is approximately 100 µM] that also inhibits differentiation of 3T3-L1 and 3T3‑F442A preadipocytes (Wright et al. 2000). BADGE administered orally at high doses to mice on a high-fat diet decreased tri glyceride content in white adipose tissue, skele- tal muscle, and the liver due to increased leptin (LEP) effects and increased fatty acid combus- tion and energy dissipation, thereby ameliorat- ing high-fat diet–induced obesity and insulin resistance (Yamauchi et al. 2001; Yun et al. Address correspondence to B. Blumberg, U.C. Irvine, 2011 BioSci 3, Irvine, CA 92697-2300, USA. Telephone: (949) 824-8573. Fax: (949) 824-4709. E-mail: blumberg@uci.edu *These authors contributed equally to this work. Supplemental Material is available online (http:// dx.doi.org/10.1289/ehp.1205063). This work was supported by a grant from the National Institutes of Health (ES-015849) to B.B. S.C.C. was supported by grant T32CA009054 from the National Cancer Institute. A.J. is a pre- doctoral trainee sponsored by the National Science Foundation’s Integrative Graduate Education and Research Traineeship program (NSF-IGERT) Life Chips Award, Division of Graduate Education (DGE) grant 0549479. B.B. is a named inventor on U.S. patents 5,861,274, 6,200,802, 6,815,168, and 7,250,273 related to PPARγ. The other authors declare they have no actual or potential competing financial interests. Received 5 February 2012; accepted 27 April 2012. 120 | number 7 | July 2012 • Environmental Health Perspectives |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::195fd353b75f34deecae5485c432f60a http://www.escholarship.org/uc/item/5637j5bc |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....195fd353b75f34deecae5485c432f60a |
| قاعدة البيانات: | OpenAIRE |
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