An in vitro approach for prioritization and evaluation of chemical effects on glucocorticoid receptor mediated adipogenesis

Toxicology and Applied Pharmacology
Jessica K HartmanRebecca A Clewell

Abstract

Rising obesity rates worldwide have socio-economic ramifications. While genetics, diet, and lack of exercise are major contributors to obesity, environmental factors may enhance susceptibility through disruption of hormone homeostasis and metabolic processes. The obesogen hypothesis contends that chemical exposure early in development may enhance adipocyte differentiation, thereby increasing the number of adipocytes and predisposing for obesity and metabolic disease. We previously developed a primary human adipose stem cell (hASC) assay to evaluate the effect of environmental chemicals on PPARG-dependent adipogenesis. Here, the assay was modified to determine the effects of chemicals on the glucocorticoid receptor (GR) pathway. In differentiation cocktail lacking the glucocorticoid agonist dexamethasone (DEX), hASCs do not differentiate into adipocytes. In the presence of GR agonists, adipocyte maturation was observed using phenotypic makers for lipid accumulation, adipokine secretion, and expression of key genes. To evaluate the role of environmental compounds on adipocyte differentiation, progenitor cells were treated with 19 prioritized compounds previously identified by ToxPi as having GR-dependent bioactivity, and multiple...Continue Reading

References

Jun 1, 1979·Journal of Pharmacokinetics and Biopharmaceutics·S E TsueiW G McBride
Apr 1, 1976·Journal of Pharmacokinetics and Biopharmaceutics·T J SullivanJ G Wagner
Sep 1, 1985·Journal of Steroid Biochemistry·D GagneD Philibert
Jan 1, 1986·European Journal of Clinical Pharmacology·D LoewE H Graul
Jan 1, 1985·European Journal of Clinical Pharmacology·H MöllmannH Derendorf
Mar 1, 1995·Journal of Clinical Pharmacology·H DerendorfM Erdmann
Oct 1, 1996·Contraception·R KekkonenP Lähteenmäki
Jul 1, 1997·Clinical Pharmacokinetics·O Heikinheimo
Jan 1, 1997·European Journal of Clinical Pharmacology·W KuhnzA Fuhrmeister
Nov 24, 1998·Journal of Clinical Pharmacology·M LeBelP K Narang
Feb 23, 2002·European Journal of Obstetrics, Gynecology, and Reproductive Biology·N N Sarkar
Dec 12, 2003·Steroids·Frank Z Stanczyk
Jan 30, 2004·Recent Progress in Hormone Research·Jonathan R SecklBrian R Walker
May 20, 2004·The Journal of Pharmacology and Experimental Therapeutics·Kouichi YoshinariMasao Miwa
Feb 25, 2005·International Journal of Clinical Pharmacology and Therapeutics·A ArancibiaW A Ritschel
Aug 5, 2005·The Journal of Endocrinology·Nicole Draper, Paul M Stewart
Oct 3, 2006·Cell Metabolism·Stephen R Farmer
Apr 28, 2007·Circulation Research·Dragomir I Draganov
May 6, 2008·Nature·Kirsty L SpaldingPeter Arner
Jun 9, 2009·Endocrine Reviews·Evanthia Diamanti-KandarakisAndrea C Gore
Dec 26, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sandrine ElleroIsabelle de Waziers
Sep 10, 2010·Environmental Health Perspectives·David M ReifRobert J Kavlock
Feb 3, 2012·Environmental Health Perspectives·Kristina A ThayerMichael A Gallo
May 15, 2013·Archives of Medical Science : AMS·Marisa CoelhoRuben Fernandes
Jun 20, 2013·Frontiers in Endocrinology·Hyokjoon Kwon, Jeffrey E Pessin
Nov 13, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Miyoung YoonHarvey J Clewell
Jun 25, 2014·Environmental Science & Technology·Daniel M RotroffRichard S Judson
Oct 25, 2014·Environmental Science & Technology·John F WambaughR Woodrow Setzer
Dec 3, 2014·Current Opinion in Pharmacology·Dayne FilerKristina Thayer
Aug 15, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Richard S JudsonRussell S Thomas
Jan 23, 2016·International Journal of Molecular Sciences·Dorothy MosetiWoo-Kyun Kim
Jul 5, 2016·International Journal of Molecular Sciences·Francisco Javier Ruiz-OjedaConcepción María Aguilera
Sep 25, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Briana FoleyChad Deisenroth

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Citations

Feb 26, 2019·Basic & Clinical Pharmacology & Toxicology·Michelle Kira Lee, Bruce Blumberg
Feb 11, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ans PuntKarma C Fussell
Sep 10, 2020·BMC Biomedical Engineering·Mallory D GriffinRosalyn D Abbott
Jan 10, 2021·The Science of the Total Environment·Hiroshi IshibashiKoji Arizono

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