Unconventional oil and gas chemicals and wastewater-impacted water samples promote adipogenesis via PPARγ-dependent and independent mechanisms in 3T3-L1 cells.

Unconventional oil and natural gas (UOG) operations have contributed to a surge in domestic oil and natural gas production in the United States, combining horizontal drilling with hydraulic fracturing to unlock previously inaccessible fossil fuel deposits. >1000 organic chemicals are used in the production process, and wastewater is produced following injection and for the life of the producing well. This wastewater is typically disposed of via injecting into disposal wells for long-term storage, treatment and discharge from wastewater treatment plants, and/or storage in open evaporation pits; however, wastewater spill rates are reported at 2-20% of active well sites across regions, increasing concerns about the environmental impacts of these wastewaters. This study assessed adipogenic activity (both triglyceride accumulation and pre-adipocyte proliferation) for a mixture of 23 commonly used UOG chemicals and a small subset of UOG wastewater-impacted surface water extracts from Colorado and West Virginia, using 3T3-L1 cells and a peroxisome proliferator activated receptor gamma (PPARγ) reporter assay. We report potent and efficacious adipogenic activity induced by both a laboratory-created UOG chemical mixture and UOG-impacted water samples at concentrations below environmental levels. We further report activation of PPARγ at similar concentrations for some samples, suggesting a causative molecular pathway for the observed effects, but not for other adipogenic samples, implicating PPARγ-dependent and independent effects from UOG associated chemicals. Taken together, these results suggest that UOG wastewater has the potential to impact metabolic health at environmentally relevant concentrations.