Effects of Crude Oil/Dispersant Mixture and Dispersant Components on PPAR γ Activity in Vitro and in Vivo : Identification of Dioctyl Sodium Sulfosuccinate (DOSS; CAS #577-11-7) as a Probable Obesogen

Abstract

BackgroundThe 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.ObjectivesWe 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.MethodsPeroxisome 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.ResultsSerum-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.ConclusionsWe conclude that DOSS is a putative obesogen worthy of further study, including epidemiological and clinical investigations into laxative prescriptions consisting of DOSS.CitationTemkin 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

An evaluation of the endocrine disruptive potential of crude oil water accommodated fractions and crude oil contaminated surface water to freshwater organisms using in vitro and in vivo approaches

“…As presently observed in X. laevis exposed to 2.5 g/L refinery oil WAF and 25 g/L bunker oil WAF, a significant increase in pparg expression was shown in marine medaka, Oryzias melastigma, exposed to crude oil WAF (20%, 5 g/L) but not in response to a lower concentration of 2.5 g/L WAF [10]. Conversely, Mississippi Canyon block 252 crude oil WAF did not induce the expression of (human) PPAR-gamma (in a mammalian cell reporter gene assay), whereas a COREXIT 9500 WAF and a COREXIT:252 oil WAF resulted in a dosedependent increase in PPARG transactivation [68].…”

Oil Spills and Human Health: Contributions of the Gulf of Mexico Research Initiative

“…Water samples were collected on two separate occasions, by the team on the NOAA research vessel Ocean Veritas (27-29 May and 2-4 June 2010), from the surface and at various depths in the GOM (Gray et al, 2014). Bowers et al (2016) and Temkin et al (2016) explored the possibility that dispersants used in the DWH cleanup effort may act as an obesogen for humans. Bowers et al (2016) and Temkin et al (2016) explored the possibility that dispersants used in the DWH cleanup effort may act as an obesogen for humans.…”

“…Bowers et al (2016) and Temkin et al (2016) explored the possibility that dispersants used in the DWH cleanup effort may act as an obesogen for humans. Because the nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ), is vital to adipocyte differentiation and is the main target of obesogens, Temkin et al (2016) used PPARγ transactivation assays to identify putative obesogens. Because the nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ), is vital to adipocyte differentiation and is the main target of obesogens, Temkin et al (2016) used PPARγ transactivation assays to identify putative obesogens.…”

Integrative and comparative reproductive biology: From alligators to xenobiotics

“…Dr. Guillette was also driven to find biomarkers capable of indicating health status and/or EDC exposure using novel analytical chemical strategies. Taking approaches commonly used in the detection of human disease states, the application of omicsbased strategies has shown considerable promise as a complimentary assay for characterizing the consequences related to EDC exposure, especially with the increasing body of knowledge that certain EDCs can affect other lesser-studied pathways (e.g., obesogens) (Temkin et al, 2015). …”