Background: The obesity pandemic is associated with multiple major health concerns. In addition to diet and lifestyle, there is increasing evidence that environmental exposures to chemicals known as obesogens also may promote obesity.

Objectives: We investigated the massive environmental contamination resulting from the Deepwater Horizon (DWH) oil spill, including the use of the oil dispersant COREXIT in remediation efforts, to determine whether obesogens were released into the environment during this incident. We also sought to improve the sensitivity of obesogen detection methods in order to guide post-toxicological chemical assessments.

Methods: Peroxisome proliferator–activated receptor gamma (PPARγ) transactivation assays were used to identify putative obesogens. Solid-phase extraction (SPE) was used to sub-fractionate the water-accommodated fraction generated by mixing COREXIT, cell culture media, and DWH oil (CWAF). Liquid chromatography–mass spectrometry (LC-MS) was used to identify components of fractionated CWAF. PPAR response element (PPRE) activity was measured in PPRE-luciferase transgenic mice. Ligand-binding assays were used to quantitate ligand affinity. Murine 3T3-L1 preadipocytes were used to assess adipogenic induction.

Results: Serum-free conditions greatly enhanced the sensitivity of PPARγ transactivation assays. CWAF and COREXIT had significant dose-dependent PPARγ transactivation activities. From SPE, the 50:50 water:ethanol volume fraction of CWAF contained this activity, and LC-MS indicated that major components of COREXIT contribute to PPARγ transactivation in the CWAF. Molecular modeling predicted several components of COREXIT might be PPARγ ligands. We classified dioctyl sodium sulfosuccinate (DOSS), a major component of COREXIT, as a probable obesogen by PPARγ transactivation assays, PPAR-driven luciferase induction in vivo, PPARγ binding assays (affinity comparable to pioglitazone and arachidonic acid), and in vitro murine adipocyte differentiation.

Conclusions: We conclude that DOSS is a putative obesogen worthy of further study, including epidemiological and clinical investigations into laxative prescriptions consisting of DOSS.

Citation: Temkin AM, Bowers RR, Magaletta ME, Holshouser S, Maggi A, Ciana P, Guillette LJ, Bowden JA, Kucklick JR, Baatz JE, Spyropoulos DD. 2016. Effects of crude oil/dispersant mixture and dispersant components on PPARγ activity in vitro and in vivo : identification of dioctyl sodium sulfosuccinate (DOSS; CAS #577-11-7) as a probable obesogen. Environ Health Perspect 124:112–119; http://dx.doi.org/10.1289/ehp.1409672

*These authors contributed equally to this work.

Address correspondence to D.D. Spyropoulos, Pathology and Laboratory Medicine, MUSC, Darby Children’s Research Institute, CRI 207, 173 Ashley Ave., Charleston, SC 29425 USA. Telephone: (843) 792-1625. E-mail: [email protected]

We are indebted to B. Blumberg, UC Irvine, and B. Abbott, U.S. Environmental Protection Agency, for providing plasmids used in PPARγ transactivation assays.

This study was supported by the Gulf of Mexico Research Initiative grant GoMR12012-11-344.

The identification of equipment and materials in this publication does not imply recommendation or endorsement by the National Institute of Standards and Technology.

A.M. and P.C. declare a potential competing financial interest regarding “repTOP^TM PPRE-Luc” mice from Transgenic Operative Products. The other authors declare they have no actual or potential competing financial interests.

Received: 31 December 2014 Accepted: 9 June 2015 Advance Publication: 2 July 2015 Final Publication: 1 January 2016

Note to readers with disabilities: EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected] . Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Note to readers with disabilities: EHP has provided a 508-conformant table of contents summarizing the Supplemental Material for this article (see below) so readers with disabilities may determine whether they wish to access the full, nonconformant Supplemental Material. If you need assistance accessing this or any other content on this site, please contact [email protected] . Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Supplemental Table of Contents PDF (177 KB)