DOI :10.26650/IstanbulJPharm.2022.1027027   IUP :10.26650/IstanbulJPharm.2022.1027027    Full Text (PDF)

Obesogens: Definition, mechanisms of action, potential industrial chemicals and pharmaceuticals

Bita EntezariDeniz BozdağHande Gürer Orhan

The incidence of obesity and related diseases has increased dramatically in the last decade. Some endocrine disruptors have been shown to interact with metabolic processes via various cellular mechanisms, and disrupt homeostasis in adipose tissue, resulting in weight gain and obesity. These chemicals are called “obesogens”. Today, with the increased use of industrial chemicals, individuals are exposed to a mixture of chemicals at very low doses. Most of these industrial chemicals have been investigated for their possible endocrine-disrupting and obesogenic effects. Besides these chemicals, pharmaceuticals can also have similar adverse effects; however, limited studies have been performed to investigate such effects of drugs. Furthermore, there are few studies investigating the relationship between prenatal exposure to pharmaceuticals and childhood obesity. Therefore, to clarify the endocrine-disrupting and obesogenic effects of the pharmaceuticals, which are prescribed during pregnancy, mechanistic studies should be performed, and necessary precautions should be taken. In this paper, we reviewed the mechanisms of obesogens, briefly overview several well-known obesogenic industrial chemicals, and focused more on potential obesogenic pharmaceuticals.

PDF View


  • Aghamohammadzadeh, N., Niafar, M., Dalir Abdolahinia, E., Na-jafipour, F., Mohamadzadeh Gharebaghi, S., Adabi, K., ... Ahadi, H. (2015). The effect of pioglitazone on weight, lipid profile and liver enzymes in type 2 diabetic patients. Therapeutic Ad-vances in Endocrinology and Metabolism, 6(2), 56-60. https://doi. org/10.1177/2042018815574229 google scholar
  • Ahmed, S., & Atlas, E. (2016). Bisphenol S- and bisphenol A-in-duced adipogenesis of murine preadipocytes occurs through direct peroxisome proliferator-activated receptor gamma acti-vation. International Journal of Obesity (2005), 40(10), 1566-1573. google scholar
  • Albaugh, V. L., Judson, J. G., She, P., Lang, C. H., Maresca, K. P., Joyal, J. L., & Lynch, C. J. (2011). Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis. Mo-lecular Psychiatry, 16(5), 569-581. Albert, O., Desdoits-Lethimonier, C., Lesne, L., Legrand, A., Guille, F., Bensalah, K., ... Jegou, B. (2013). Paracetamol, aspirin and in-domethacin display endocrine disrupting properties in the adult human testis in vitro. Human Reproduction (Oxford, England), 28(7), 1890-1898. google scholar
  • Alonso-Magdalena, P., Laribi, O., Ropero, A. B., Fuentes, E., Ripoll, C., Soria, B., & Nadal, A. (2005). Low doses of bisphenol A and di-ethylstilbestrol impair Ca2+ signals in pancreatic a-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans. Environmental Health Perspectives, 113(8), 969-977. google scholar
  • Arterburn, D., Sofer, T., Boudreau, D., Bogart, A., Westbrook, E., Theis, M., . Haneuse, S. (2016). Long-Term Weight Change after Initiating Second-Generation Antidepressants. Journal of Clinical Medicine, 5(4), 48-60. google scholar
  • Atli, O., Baysal, M., Aydogan-Kilic, G., Kilic, V., Ucarcan, S., Kara-duman, B., & Ilgin, S. (2017). Sertraline-induced reproductive toxicity in male rats: Evaluation of possible underlying mecha-nisms. Asian Journal of Andrology, 19(6), 672-679. https://doi. org/10.4103/1008-682X.192637 google scholar
  • Autrup, H., Barile, F. A., Berry, S. C., Blaauboer, B. J., Boobis, A., Bolt, H., . Vermeulen, N. P. (2020). Human exposure to synthetic en-docrine disrupting chemicals (S-EDCs) is generally negligible as compared to natural compounds with higher or comparable en-docrine activity. How to evaluate the risk of the S-EDCs? Toxicol-ogy in Vitro, 67, 104861."> Baillie-Hamilton, P. F. (2002). Chemical toxins: A hypothesis to explain the global obesity epidemic. Journal of Alterna-tive and Complementary Medicine, 8(2), 185-192. https://doi. org/10.1089/107555302317371479 google scholar
  • Bashshur, R. L., Mandil, S. H., & Shannon, G. W. (2002). Global as-sessment of the state-of-the-science of endocrine disruptors -Chapter 1: Executive summary. Telemedicine Journal and E-Health, 8(1), 95-107. google scholar
  • Bastos Sales, L., Kamstra, J. H., Cenijn, P. H., van Rijt, L. S., Hamers, T., & Legler, J. (2013). Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation. Toxicology in Vitro, 27(6), 1634-1643. TIV.2013.04.005 google scholar
  • Blumenthal, S. R., Castro, V. M., Clements, C. C., Rosenfield, H. R., Murphy, S. N., Fava, M., . Perlis, R. H. (2014). An electronic health records study of long-term weight gain following antidepressant use. JAMA Psychiatry, 71(8), 889-896. google scholar
  • Buck Louis, G. M., Chen, Z., Kim, S., Smarr, M. M., & Kannan, K. (2017). Male urinary paracetamol and semen quality. Andrology, 5(6), 1082-1088. google scholar
  • Casals-Casas, C., & Desvergne, B. (2011). Endocrine Disruptors: From Endocrine to Metabolic Disruption. Annual Review of Physi-ology, 73(1), 135-162. google scholar
  • Chamorro-Garcia, R., Diaz-Castillo, C., Shoucri, B. M., Kach, H., Leavitt, R., Shioda, T., & Blumberg, B. (2017). Ancestral perina-tal obesogen exposure results in a transgenerational thrifty phenotype in mice. Nature Communications, 8(1). https://doi. org/10.1038/s41467-017-01944-z google scholar
  • Chamorro-Garca, R., Sahu, M., Abbey, R. J., Laude, J., Pham, N., & Blumberg, B. (2013). Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal exposure to the obesogen tributyltin in mice. Environmental Health Perspectives, 121(3), 359-366. https://doi. org/10.1289/ehp.1205701 google scholar
  • Chawla, S., Kaushik, N., Singh, N. P., Ghosh, R. K., & Saxena, A. (2013). Effect of addition of either sitagliptin or pioglitazone in patients with uncontrolled type 2 diabetes mellitus on metfor-min: A randomized controlled trial. Journal of Pharmacology and Pharmacotherapeutics, 4(1), 27-32. google scholar
  • Chu, D. T., Malinowska, E., Jura, M., & Kozak, L. P. (2017). C57BL/6J mice as a polygenic developmental model of diet-induced obesity. Physi-ological Reports, 5(7), e13093. Cohen, I. C., Cohenour, E. R., Harnett, K. G., & Schuh, S. M. (2021). BPA, BPAF and TMBPF Alter Adipogenesis and Fat Accumulation in Human Mesenchymal Stem Cells, with Implications for Obesi-ty. International Journal of Molecular Sciences, 22(10), 5363. https:// google scholar
  • Darbre, P. D. (2017). Endocrine Disruptors and Obesity. Current Obesity Reports, 6(1), 18-27. google scholar
  • Davis, K. E., Carstens, E. J., Irani, B. G., Gent, L. M., Hahner, L. M., & Clegg, D. J. (2014). Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis. Hormones and Behavior, Vol. 66, pp. 196-207. Academic Press Inc. google scholar
  • De Cock, M., & Van de Bor, M. (2014). Obesogenic effects of endocrine disruptors, what do we know from animal and hu-man studies? Environment International, 70, 15-24. https://doi. org/10.1016/j.envint.2014.04.022 google scholar
  • Feige, J. N., Gelman, L., Rossi, D., Zoete, V., Metivier, R., Tudor, C., . Desvergne, B. (2007). The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis. The Journal of Biological Chemistry, 282(26), 19152-19166. https://doi. org/10.1074/JBC.M702724200 google scholar
  • Foley, B., Clewell, R., & Deisenroth, C. (2015). Development of a Human Adipose-Derived Stem Cell Model for Characterization of Chemical Modulation of Adipogenesis. Applied In Vitro Toxicology, 1(1), 66-78. google scholar
  • Fürnsinn, C., & Waldhausl, W. (2002). Thiazolidinediones: Meta-bolic actions in vitro. Diabetologia, Vol. 45, pp. 1211-1223. https:// google scholar
  • Gafoor, R., Booth, H. P., & Gulliford, M. C. (2018). Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: Population based cohort study. BMJ (Online), 361. https://doi. org/10.1136/bmj.k1951 google scholar
  • Greenberg, E. R., Barnes, A. B., Resseguie, L., Barrett, J. A., Burn-side, S., Lanza, L. L., . Colton, T. (1984). Breast Cancer in Moth-ers Given Diethylstilbestrol in Pregnancy. New England Jour-nal of Medicine, 311(22), 1393-1398. nejm198411293112201 google scholar
  • Gregorian Jr, R. S., Golden, K. A., Bahce, A., Goodman, C., & Kwong, W. J. (2002). Antidepressant-Induced Sexual Dysfunction. The Annals of pharmacotherapy, 36(10), 1577-1589. https://doi. org/10.1345/aph.1A195. google scholar
  • Griffin, M. D., Pereira, S. R., DeBari, M. K., & Abbott, R. D. (2020). Mechanisms of action, chemical characteristics, and model systems of obesogens. BMC Biomedical Engineering, 2(1), 1-13. google scholar
  • Grün, F., & Blumberg, B. (2006a). Environmental obesogens: Or-ganotins and endocrine disruption via nuclear receptor signaling. Endocrinology, Vol. 147."> Grün, F., Watanabe, H., Zamanian, Z., Maeda, L., Arima, K., Cubacha, R.,... Blumberg, B. (2006b). Endocrine-disrupting organotin com-pounds are potent inducers of adipogenesis in vertebrates. Mo-lecular Endocrinology, 20(9), 2141-2155. me.2005-0367 google scholar
  • Gupta, R., Kumar, P., Fahmi, N., Garg, B., Dutta, S., Sachar, S., . Vimaleswaran, K. S. (2020). Endocrine disruption and obesity: A current review on environmental obesogens. Current Research in Green and Sustainable Chemistry, 3. CRGSC.2020.06.002 google scholar
  • Haliakon, S., Doare, L., Foufelle, F., Kergoat, M., Guerre-Millo, M., Berthault, M.-F., . Ferre, P. (1997). Pioglitazone Induces In Vivo Adipocyte Differentiation in the Obese Zucker fa/fa Rat. Diabetes, 46(9), 1393-1399. google scholar
  • Hansen, C. H., Larsen, L. W., S0rensen, A. M., Halling-S0rensen, B., & Styrishave, B. (2017). The six most widely used selective serotonin reuptake inhibitors decrease androgens and increase estrogens in the H295R cell line. Toxicology in Vitro, 41, 1-11. https://doi. org/10.1016/j.tiv.2017.02.001 google scholar
  • Hao, C., Cheng, X., Guo, J., Xia, H., & Ma, X. (2013). Perinatal exposure to diethyl-hexyl-phthalate induces obesity in mice. Frontiers in Bio-science (Elite Edition), 5(2), 725-733. Hao, C. J., Cheng, X. J., Xia, H. F., & Ma, X. (2012a). The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice. Toxicology and Applied Pharmacology, 263(1), 102-110. google scholar
  • Hao, C. J., Cheng, X. J., Xia, H. F., & Ma, X. (2012b). The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice. Toxicology and Applied Pharmacology, 263(1), 102-110. Hatch, E. E., Troisi, R., Palmer, J. R., Wise, L. A., Titus, L., Strohsnitter, W. C., . Hoover, R. N. (2014). Prenatal diethylstilbestrol exposure and risk of obesity in adult women. Journal of Developmental Ori-gins of Health and Disease, 6(3), 201-207. S2040174415000033 google scholar
  • Hausman, G. J., Poulos, S. P., Pringle, T. D., & Azain, M. J. (2008). The influence of thiazolidinediones on adipogenesis in vitro and in vivo: potential modifiers of intramuscular adipose tissue deposi-tion in meat animals. Journal of Animal Science, Vol. 86. https://doi. org/10.2527/jas.2007-0219 google scholar
  • Heitzer, M. D., Wolf, I. M., Sanchez, E. R., Witchel, S. F., & DeFran-co, D. B. (2007). Glucocorticoid receptor physiology. Reviews in Endocrine and Metabolic Disorders, Vol. 8, pp. 321-330. Springer. google scholar
  • Hill, J. O., Wyatt, H. R., & Peters, J. C. (2012). Energy balance and obesity. Circulation, 126(1), 126-132. google scholar
  • Homma, H., Kurachi, H., Nishio, Y., Takeda, T., Yamamoto, T., Adachi, K., . Murata, Y. (2000). Estrogen suppresses transcription of lipopro-tein lipase gene. Existence of a unique estrogen response element on the lipoprotein lipase promoter. Journal of Biological Chemistry, 275(15), 11404-11411. google scholar
  • Hoover, R. N., Hyer, M., Pfeiffer, R. M., Adam, E., Bond, B., Cheville, A. L., . Troisi, R. (2011). Adverse Health Outcomes in Women Ex-posed In Utero to Diethylstilbestrol. New England Journal of Medi-cine, 365(14), 1304-1314. Jacobsen, N. W., Hansen, C. H., Nellemann, C., Styrishave, B., & Hal-ling-S0rensen, B. (2015). Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay. Toxicology in Vitro, 29(7), 1729-1735. google scholar
  • Janesick, A., & Blumberg, B. (2012). Obesogens, stem cells and the developmental programming of obesity. International Journal of Andrology, Vol. 35, pp. 437-448. NIH Public Access. https://doi. org/10.1111/j.1365-2605.2012.01247.x google scholar
  • Janesick, A. S., Dimastrogiovanni, G., Vanek, L., Boulos, C., Cham-orro-Garc(a, R., Tang, W., & Blumberg, B. (2016). On the utility of ToxCastTM and ToxPi as methods for identifying new obesogens. Environmental Health Perspectives, 124(8), 1214-1226. https://doi. org/10.1289/ehp.1510352 google scholar
  • Janesick, Amanda, & Blumberg, B. (2011). Endocrine disrupting chemicals and the developmental programming ofadipogenesis and obesity. Birth Defects Research Part C: Embryo Today: Reviews, 93(1), 34-50. google scholar
  • Jensen, E. T., & Longnecker, M. P. (2014). Pharmacologic sex hor-mones in pregnancy in relation to offspring obesity. Obesity, 22(11), 2406-2412. google scholar
  • Kanayama, T., Kobayashi, N., Mamiya, S., Nakanishi, T., & Nishikawa, J. I. (2005). Organotin compounds promote adipocyte differentia-tion as agonists of the peroxisome proliferator-activated recep-tor Y/retinoid X receptor pathway. Molecular Pharmacology, 67 (3), 766-774. google scholar
  • Kersten, S. (2001). Mechanisms of nutritional and hormonal regu-lation of lipogenesis. EMBO Reports, 2(4), 282-286. https://doi. org/10.1093/embo-reports/kve071 google scholar
  • Kirchner, S., Kieu, T., Chow, C., Casey, S., & Blumberg, B. (2010). Pre-natal exposure to the environmental obesogen tributyltin predis-poses multipotent stem cells to become adipocytes. Molecular En-docrinology, 24(3), 526-539. Koya, D., & Kanasaki, K. (2011). Biology of obesity: Lessons from animal models of obesity. Journal of Biomedicine and Biotechnol-ogy, Vol. 2011. google scholar
  • La Merrill, M. A., Vandenberg, L. N., Smith, M. T., Goodson, W., Browne, P., Patisaul, H. B., . Zoeller, R. T. (2020). Consensus on the key characteristics ofendocrine-disrupting chemicals as a ba-sis for hazard identification. Nature Reviews Endocrinology, 16(1), 45-57. google scholar
  • La Merrill, M., & Birnbaum, L. S. (2011). Childhood obesity and environmental chemicals. Mount Sinai Journal of Medicine, 78(1), 22-48. google scholar
  • Lebovitz, H. E. (2019). Thiazolidinediones: the Forgotten Diabetes Medications. Current Diabetes Reports, Vol. 19, pp. 1-13. Springer. google scholar
  • Lefterova, M. I., & Lazar, M. A. (2009). New developments in adipo-genesis. Trends in Endocrinology and Metabolism, 20(3), 107-114. google scholar
  • Lehmann, J. M., Moore, L. B., Smith-Oliver, T. A., Wilkison, W. O., Will-son, T. M., & Kliewer, S. A. (1995). An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated re-ceptor y (PPARy). Journal of Biological Chemistry, 270(22), 1295312956. google scholar
  • Li, X., Ycaza, J., & Blumberg, B. (2011). The environmental obeso-gen tributyltin chloride acts via peroxisome proliferator activated receptor gamma to induce adipogenesis in murine 3T3-L1 pre-adipocytes. Journal of Steroid Biochemistry and Molecular Biology, 127(1-2), 9-15. google scholar
  • Liew, Z., Nohr, E. A., Morgen, C. S., Ernst, A., Li, J., S0rensen, T. I. A., & Olsen, J. (2019). Prenatal Exposure to Acetaminophen and Overweight in Childhood. Obesity, 27(8), 1314-1322. https://doi. org/10.1002/oby.22526 google scholar
  • Lind, D. V., Main, K. M., Kyhl, H. B., Kristensen, D. M., Toppari, J., An-dersen, H. R., . Jensen, T. K. (2017). Maternal use of mild analgesics during pregnancy associated with reduced anogenital distance in sons: A cohort study of 1027 mother-child pairs. Human Reproduc-tion, 32(1), 223-231. google scholar
  • Lord, C. C., Wyler, S. C., Wan, R., Castorena, C. M., Ahmed, N., Mathew, D., ... Elmquist, J. K. (2017). Atypical antipsychotic causes weight gain by targeting serotonin receptor 2C. Clinical Pharma-cist, 9(10), 3402-3406. google scholar
  • MacKay, H., & Abizaid, A. (2018). A plurality of molecular targets: The receptor ecosystem for bisphenol-A (BPA). Hormones and Behavior, 101(November), 59-67. google scholar
  • Maloney, E. K., & Waxman, D. J. (1999). trans-Activation of PPA-Ralpha and PPARgamma by structurally diverse environmental chemicals. Toxicology and Applied Pharmacology, 161(2), 209-218. google scholar
  • Manikkam, M., Tracey, R., Guerrero-Bosagna, C., & Skinner, M. K. (2013). Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PloS One, 8(1). google scholar
  • Masuno, H., Kidani, T., Sekiya, K., Sakayama, K., Shiosaka, T., Yama-moto, H., & Honda, K. (2002). Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes. Journal of Lipid Research, 43(5), 676-684. https://doi. org/10.1016/S0022-2275(20)30108-5 google scholar
  • Mauvais-Jarvis, F. (2011). Estrogen and androgen receptors: Regu-lators of fuel homeostasis and emerging targets for diabetes and obesity. Trends Endocrinol Metab, 22(1), 24-33. https://doi. org/10.1016/j.tem.2010.10.002 google scholar
  • McTernan, P. G., Harte, A. L., Anderson, L. A., Green, A., Smith, S. A., Holder, J. C., . Kumar, S. (2002). Insulin and rosiglitazone regulation of lipolysis and lipogenesis in human adipose tissue in vitro. Diabetes, 51(5), 1493-1498. google scholar
  • Miettinen, S., Sarkanen, J. R., & Ashammakhi, N. (2008). Adipose Tissue and Adipocyte Differentiation: Molecular and Cellular As-pects and Tissue Engineering Applications. Topics in Tissue Engi-neering, 4, 1-26. google scholar
  • Moazzam, S., Jarmasz, J. S., Jin, Y., Siddiqui, T. J., & Cattini, P. A. (2021). Effects of high fat diet-induced obesity and pregnancy on prepartum and postpartum maternal mouse behavior. Psy-choneuroendocrinology, 126, 105147. psyneuen.2021.105147 google scholar
  • Montagnini, B. G., Bortolan, S., Santos, B. D. Dos, Moreno, A. P., De Azevedo Camin, N., Gerardin, D. C. C., & Moreira, E. G. (2013). Eval-uation of escitalopram, sertraline, and methylphenidate in the immature rat uterotrophic assay. International Journal of Toxicol-ogy, 32(6), 426-430. google scholar
  • Moraitis, A. G., Block, T., Nguyen, D., & Belanoff, J. K. (2017, Janu-ary 1). The role of glucocorticoid receptors in metabolic syn-drome and psychiatric illness. Journal of Steroid Biochemistry and Molecular Biology, Vol. 165, pp. 114-120. Elsevier Ltd. https://doi. org/10.1016/j.jsbmb.2016.03.023 google scholar
  • Mori, Y., Murakawa, Y., Okada, K., Horikoshi, H., Yokoyama, J., Ta-jima, N., & Ikeda, Y. (1999). Effect of troglitazone on body fat distri-bution in type 2 diabetic patients. Diabetes Care, 22(6), 908-912. google scholar
  • Moseti, D., Regassa, A., & Kim, W. K. (2016). Molecular regulation of adipogenesis and potential anti-adipogenic bioactive molecules. International Journal of Molecular Sciences, 17(1), 1-24. https://doi. org/10.3390/ijms17010124 google scholar
  • Müller, J. C., Imazaki, P. H., Boareto, A. C., Lourenço, E. L. B., Golin, M., Vechi, M. F., . Dalsenter, P. R. (2012). In vivo and in vitro estrogen-ic activity of the antidepressant fluoxetine. Reproductive Toxicol-ogy, 34(1), 80-85. google scholar
  • Munkboel, C. H., Larsen, L. W., Weisser, J. J., Kristensen, D. M., & Styrishave, B. (2018). Sertraline suppresses testis and adrenal steroid production and steroidogenic gene expression while increasing LH in Plasma of male rats resulting in compensatory hypogonadism. Toxicological Sciences, 163(2), 609-619. https:// google scholar
  • Murphy, R., Stewart, A. W., Braithwaite, I., Beasley, R., Hancox, R. J., & Mitchell, E. A. (2015). Association between paracetamol use in infancy or childhood with body mass index. Obesity, 23(5), 10301038. google scholar
  • Newbold, R. R., Padilla-Banks, E., Jefferson, W. N., & Heindel, J. J. (2008). Effects of endocrine disruptors on obesity. International Journal of Andrology, 31(2), 201-207. j.1365-2605.2007.00858.x google scholar
  • Newbold, R. R., Padilla-banks, E., Snyder, R. J., & Jefferson, W. N. (2005). Developmental Exposure to Estrogenic Compounds and Obesity. 480, 478-480. google scholar
  • Newbold, R. R., Padilla-Banks, E., Snyder, R. J., & Jefferson, W. N. (2007a). Perinatal exposure to environmental estrogens and the development of obesity. Molecular Nutrition and Food Research, Vol. 51, pp. 912-917. Newbold, R. R., Padilla-Banks, E., Snyder, R. J., Phillips, T. M., & Jef-ferson, W. N. (2007b). Developmental exposure to endocrine dis-ruptors and the obesity epidemic. Reproductive Toxicology, Vol. 23, pp. 290-296. google scholar
  • Obri, A., Serra, D., Herrero, L., & Mera, P. (2020). The role of epi-genetics in the development of obesity. Biochemical Pharmacol-ogy, Vol. 177, p. 113973. Elsevier Inc. bcp.2020.113973 google scholar
  • OECD. (2012). OECD Detailed review paper on the state of the science on novel in vitro and in vivo screening and testing methods and endpoints for evaluating endocrine disruptors OECD Environment, Health and Safety Publica-tions Series on Testing and Assessment 2012 Par. Retrieved November 6, 2021, from docserver/9789264221352-en.pdf?expires=1636196089&id=i d&accname=guest&checksum=960E616120F388C1D44E902 319C840AC google scholar
  • Palin, S. L., McTernan, P. G., Anderson, L. A., Sturdee, D. W., Bar-nett, A. H., & Kumar, S. (2003). 17p-Estradiol and anti-estrogen ICI:compound 182,780 regulate expression of lipoprotein lipase and hormone-sensitive lipase in isolated subcutaneous abdomi-nal adipocytes. Metabolism: Clinical and Experimental, 52(4), 383388. google scholar
  • Palmer, J. R., Herbst, A. L., Noller, K. L., Boggs, D. A., Troisi, R., Titus-Ernstoff, L., . Hoover, R. N. (2009). Urogenital abnormalities in men exposed to diethylstilbestrol in utero: A cohort study. Envi-ronmental Health: A Global Access Science Source, 8, 37. https://doi. org/10.1186/1476-069X-8-37 google scholar
  • Pedersen, S. B., B0rglum, J. D., M011er-Pedersen, T., & Richelsen, B. (1992). Effects of in vivo estrogen treatment on adipose tissue metabolism and nuclear estrogen receptor binding in isolated rat adipocytes. Molecular and Cellular Endocrinology, 85(1-2), 13-19. google scholar
  • Peeke, P. M., & Chrousos, G. P. (1995). Hypercortisolism and Obe-sity. Annals of the New York Academy of Sciences, 771(1), 665-676. google scholar
  • Piersma, A. H., Luijten, M., Popov, V., Tomenko, V., Altstein, M., Kagampang, F., & Schlesinger, H. (2009). Pharmaceuticals. In En-docrine-Disrupting Chemicals in Food (pp. 459-518). Elsevier Ltd. google scholar
  • Raeder, M. B., Fern0, J., Vik-Mo, A. O., & Steen, V. M. (2006). SREBP activation by antipsychotic- and antidepressant-drugs in cul-tured human liver cells: Relevance for metabolic side-effects? Molecular and Cellular Biochemistry, 289(1-2), 167-173. https:// google scholar
  • Rask, E., Olsson, T., Söderberg, S., Andrew, R., Livingstone, D. E. W., Johnson, O., & Walker, B. R. (2001). Tissue-specific dysregula-tion of cortisol metabolism in human obesity. Journal of Clinical Endocrinology and Metabolism, 86(3), 1418-1421. https://doi. org/10.1210/jcem.86.3.7453 google scholar
  • Richard, A. J., White, U., Elks, C. M., & Stephens, J. M. (2000). Adi-pose Tissue: Physiology to Metabolic Dysfunction. In Endotext., Inc. Retrieved from pubmed/32255578 google scholar
  • Rissman, E. F., & Adli, M. (2014). Minireview: Transgenerational Epi-genetic Inheritance: Focus on Endocrine Disrupting Compounds. Endocrinology, 155(8), 2770. Ritchie, H., & Max, R. (2017). Obesity - Our World in Data. Retrieved November 4, 2021, from google scholar
  • Romao, J. M., & Guan, L. L. (2014). Adipogenesis and Obesity. In MicroRNA in Regenerative Medicine (pp. 539-565). Elsevier Inc. google scholar
  • Rönn, M., Lind, L., Örberg, J., Kullberg, J., Söderberg, S., Larsson, A., ... Lind, P M. (2014). Bisphenol A is related to circulating lev-els of adiponectin, leptin and ghrelin, but not to fat mass or fat distribution in humans. Chemosphere, 112, 42-48. https://doi. org/10.1016/J.CHEMOSPHERE.2014.03.042 google scholar
  • Rosen, E. D., & MacDougald, O. A. (2006). Adipocyte differentiation from the inside out. Nature Reviews Molecular Cell Biology, 7(12), 885-896. google scholar
  • Rubin, B. S., Paranjpe, M., DaFonte, T., Schaeberle, C., Soto, A. M., Obin, M., & Greenberg, A. S. (2017). Perinatal BPA exposure alters body weight and composition in a dose specific and sex specific manner: The addition of peripubertal exposure exacerbates ad-verse effects in female mice. Reproductive Toxicology (Elmsford, N.Y.), 68, 130-144. Safarinejad, M. R. (2008). Evaluation of endocrine profile and hypothalamic-pituitary-testis axis in selective serotonin reuptake inhibitor-induced male sexual dysfunction. Journal of Clinical Psychopharmacology, 28(4), 418-423. JCP.0b013e31817e6f80 google scholar
  • Sarjeant, K., & Stephens, J. M. (2012). Adipogenesis. Cold Spring Harbor Perspectives in Biology, 4(9), a008417. google scholar
  • Schrager, S., & Potter, B. E. (2004). Diethylstilbestrol Exposure - Amer-ican Family Physician. Retrieved from google scholar
  • Sharma, G., Hu, C., Brigman, J. L., Zhu, G., Hathaway, H. J., & Prossnitz, E. R. (2013). GPER deficiency in male mice results in in-sulin resistance, dyslipidemia, and a proinflammatory state. Endo-crinology, 154(11), 4136-4145. google scholar
  • Sharma, G., & Prossnitz, E. R. (2017). G-protein-coupled estro-gen receptor (GPER) and sex-specific metabolic homeostasis. In Advances in Experimental Medicine and Biology. 1043, 427-453. google scholar
  • Sharma, G., & Prossnitz, E. R. (2021). Targeting the G protein-cou-pled estrogen receptor (GPER) in obesity and diabetes. Endocrine and Metabolic Science, 2, 100080. google scholar
  • Somm, E., Schwitzgebel, V. M., Toulotte, A., Cederroth, C. R., Combescure, C., Nef, S., . Hüppi, P. S. (2009). Perinatal exposure to bisphenol A alters early adipogenesis in the rat. Environmental Health Perspectives, 117(10), 1549-1555. Stahlhut, R. W., Wijngaarden, E. van, Dye, T. D., Stephen, C., & Swan, S. H. (2007). Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males. Environmental Health Perspectives, 115(6), 876-882. google scholar
  • Stel, J., & Legler, J. (2015). The role of epigenetics in the latent effects of early life exposure to obesogenic endocrine disrupt-ing chemicals. Endocrinology, 156(10), 3466-3472. https://doi. org/10.1210/EN.2015-1434 google scholar
  • Stger, R. (2008). Epigenetics and obesity. Pharmacogenomics, Vol. 9, pp. 1851-1860. google scholar
  • Tafuri, S. R. (1996). Troglitazone Enhances Differentiation, Basal Glucose Uptake, and Glut1 Protein Levels in 3T3-Ll Adipo-cytes. Retrieved from google scholar
  • USEPA. (2021). What is the Endocrine System? | US EPA. Retrieved November 6, 2021, from google scholar
  • Verhaegen, A. A., & Van Gaal, L. F. (2017). Drug-induced obesity and its metabolic consequences: a review with a focus on mech-anisms and possible therapeutic options. Journal of Endocrino-logical Investigation, 40(11), 1165-1174. s40618-017-0719-6 google scholar
  • Vernon, R. G., & David J. Flint. (2011). Adipose tissue. Journal Fur Asthetische Chirurgie, 4(1), 28-34. google scholar
  • Wake, D. J., Rask, E., Livingstone, D. E. W., So"derberg, S., So"derberg, S., Olsson, T., & Walker, B. R. (2003). COMMENT Local and Systemic Impact of Transcriptional Up-Regulation of 11-Hydroxysteroid Dehy-drogenase Type 1 in Adipose Tissue in Human Obesity. https://doi. org/10.1210/jc.2003-030286 google scholar
  • WHO. (2021). WHO. Retrieved May 15, 2021, from World Health Organization website: google scholar
  • Wu, Z., Bucher, N. L., & Farmer, S. R. (1996). Induction of peroxi-some proliferator-activated receptor gamma during the conver-sion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids. Molecular and Cellular Biology, 16(8), 4128-4136. google scholar
  • Yang, C., Lee, H. K., Kong, A. P. S., Lim, L. L., Cai, Z., & Chung, A. C. K. (2018). Early-life exposure to endocrine disrupting chemicals as-sociates with childhood obesity. Annals of Pediatric Endocrinology and Metabolism, Vol. 23, pp. 182-195. Korean society of pediatric endocrinology. google scholar
  • Yang, L.-H., Chen, T.-M., Yu, S.-T., & Chen, Y.-H. (2007). Olanzapine induces SREBP-1-related adipogenesis in 3T3-L1 cells. Pharma-cological Research, 56(3), 202-208. PHRS.2007.05.007 google scholar
  • Zhu, P., Yuen, J. M. L., Sham, K. W. Y., & Cheng, C. H. K. (2013). GPER mediates the inhibitory actions of estrogen on adipogenesis in 3T3-L1 cells through perturbation of mitotic clonal expansion. General and Comparative Endocrinology, 193, 19-26. https://doi. org/10.1016/j.ygcen.2013.07.004 google scholar


Copy and paste a formatted citation or use one of the options to export in your chosen format



Entezari, B., Bozdağ, D., & Gürer Orhan, H. (2022). Obesogens: Definition, mechanisms of action, potential industrial chemicals and pharmaceuticals. İstanbul Journal of Pharmacy, 52(2), 215-225.


Entezari B, Bozdağ D, Gürer Orhan H. Obesogens: Definition, mechanisms of action, potential industrial chemicals and pharmaceuticals. İstanbul Journal of Pharmacy. 2022;52(2):215-225.


Entezari, B.; Bozdağ, D.; Gürer Orhan, H. Obesogens: Definition, mechanisms of action, potential industrial chemicals and pharmaceuticals. İstanbul Journal of Pharmacy, [Publisher Location], v. 52, n. 2, p. 215-225, 2022.

Chicago: Author-Date Style

Entezari, Bita, and Deniz Bozdağ and Hande Gürer Orhan. 2022. “Obesogens: Definition, mechanisms of action, potential industrial chemicals and pharmaceuticals.” İstanbul Journal of Pharmacy 52, no. 2: 215-225.

Chicago: Humanities Style

Entezari, Bita, and Deniz Bozdağ and Hande Gürer Orhan. Obesogens: Definition, mechanisms of action, potential industrial chemicals and pharmaceuticals.” İstanbul Journal of Pharmacy 52, no. 2 (Mar. 2024): 215-225.

Harvard: Australian Style

Entezari, B & Bozdağ, D & Gürer Orhan, H 2022, 'Obesogens: Definition, mechanisms of action, potential industrial chemicals and pharmaceuticals', İstanbul Journal of Pharmacy, vol. 52, no. 2, pp. 215-225, viewed 3 Mar. 2024,

Harvard: Author-Date Style

Entezari, B. and Bozdağ, D. and Gürer Orhan, H. (2022) ‘Obesogens: Definition, mechanisms of action, potential industrial chemicals and pharmaceuticals’, İstanbul Journal of Pharmacy, 52(2), pp. 215-225. (3 Mar. 2024).


Entezari, Bita, and Deniz Bozdağ and Hande Gürer Orhan. Obesogens: Definition, mechanisms of action, potential industrial chemicals and pharmaceuticals.” İstanbul Journal of Pharmacy, vol. 52, no. 2, 2022, pp. 215-225. [Database Container],


Entezari B, Bozdağ D, Gürer Orhan H. Obesogens: Definition, mechanisms of action, potential industrial chemicals and pharmaceuticals. İstanbul Journal of Pharmacy [Internet]. 3 Mar. 2024 [cited 3 Mar. 2024];52(2):215-225. Available from: doi: 10.26650/IstanbulJPharm.2022.1027027


Entezari, Bita - Bozdağ, Deniz - Gürer Orhan, Hande. Obesogens: Definition, mechanisms of action, potential industrial chemicals and pharmaceuticals”. İstanbul Journal of Pharmacy 52/2 (Mar. 2024): 215-225.


Published Online29.08.2022


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.