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
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.
1Marine Biomedical Sciences Program, and 2Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA; 3Department of Chemistry, Rollins College, Winter Park, Florida, USA; 4Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA; 5Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy; 6Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, South Carolina, USA; 7National Oceanic and Atmospheric Administration, and; 8National Institute of Standards and Technology, Charleston, South Carolina, USA; 9Department of Pediatrics and Neonatology, Medical University of South Carolina, Charleston, South Carolina, USA
Recommended Citation:
Alexis M. Temkin,1* Robert R. Bowers,2* Margaret E. Magaletta,et al. 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[J]. Environmental Health Perspectives,2016-01-01,Volume 124(Issue 1):112