title: 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.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  BACKGROUND
  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.
authors.affiliation: Marine Biomedical Sciences Program, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Temkin
authors.forename: Robert R
authors.initials: RR
authors.lastname: Bowers
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Magaletta
authors.forename: Steven
authors.initials: S
authors.lastname: Holshouser
authors.forename: Adriana
authors.initials: A
authors.lastname: Maggi
authors.forename: Paolo
authors.initials: P
authors.lastname: Ciana
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Guillette
authors.forename: John A
authors.initials: JA
authors.lastname: Bowden
authors.forename: John R
authors.initials: JR
authors.lastname: Kucklick
authors.forename: John E
authors.initials: JE
authors.lastname: Baatz
authors.forename: Demetri D
authors.initials: DD
authors.lastname: Spyropoulos
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002853:Chromatography, Liquid; D004143:Dioctyl Sulfosuccinic Acid / Q000633:toxicity; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000139:chemically induced / Q000453:epidemiology* / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D010578:Petroleum / Q000633:toxicity*; D016133:Polymerase Chain Reaction
chemical_list: D047495:PPAR gamma; D010578:Petroleum; D004143:Dioctyl Sulfosuccinic Acid