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

Abstract

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.

Endocrine-Mediated Mechanisms of Metabolic Disruption and New Approaches to Examine the Public Health Threat

“…Increased risks of obesity in human adults exposed prenatally to DES have also been reported (34), delineating apparent translational effects. Our lab has recently demonstrated that common chemicals and environmental mixtures associated with unconventional oil and gas (UOG) operations can activate the peroxisome proliferator activated receptor gamma (PPARγ) and promote triglyceride accumulation and pre-adipocyte proliferation in vitro (35), and that gestational exposure to a mixture of UOG chemicals resulted in increased body weights through weaning in a rodent model (36, 37). UOG development has also been associated with increased prevalence of low birth weight and small for gestational age births in the Northeast US (38), and decreased prevalence of low birth weights and increased risk of higher birth weight babies in Colorado (39); both low (40, 41) and high (42, 43) birth weights are associated with greater risks for obesity later in life.…”

“…We further documented AR and TR antagonist activities in surface, ground, and/or drinking water near UOG operations in several regions, including CO, WY, WV, and ND [(268), Kassotis et al, in preparation, (269–271)], and evaluated a mixture of 23 common UOG chemicals via a gestational exposure experiment in C57 mice, reported putative metabolic effects (offspring exhibited increased body weights, among other effects) (36, 37). We further interrogated this by evaluating the ability of this 23-mix, several UOG wastewater samples, and several UOG wastewater-impacted surface water samples to stimulate adipogenesis in 3T3-L1 cells and activate PPARγ in a reporter gene assay (35). We demonstrated that UOG wastewater samples exhibited significant triglyceride accumulation and/or pre-adipocyte proliferation at relative water concentrations as low as 0.001x, UOG-impacted surface water extracts at concentrations as low as 0.04x, and the 23-mix at 1 μM; these effects co-occurred with PPARγ activation for some samples but not others (35), suggesting differing mechanisms.…”

“…We further interrogated this by evaluating the ability of this 23-mix, several UOG wastewater samples, and several UOG wastewater-impacted surface water samples to stimulate adipogenesis in 3T3-L1 cells and activate PPARγ in a reporter gene assay (35). We demonstrated that UOG wastewater samples exhibited significant triglyceride accumulation and/or pre-adipocyte proliferation at relative water concentrations as low as 0.001x, UOG-impacted surface water extracts at concentrations as low as 0.04x, and the 23-mix at 1 μM; these effects co-occurred with PPARγ activation for some samples but not others (35), suggesting differing mechanisms. Related work demonstrated highly efficacious triglyceride accumulation for various non-ionic alkylphenol and alcohol polyethoxylates in the absence of PPARγ activation and potentially mediated by TR antagonism (272).…”

Preparation of cellulose triacetate aerogel via non‐solvent impacted thermally induced phase separation for oil absorption

“…[4,5] Therefore, numerous technologies have been developed to deal with this water pollution, such as magnetic separation, chemical dispersant, absorption and biological treatment. [6][7][8] Among those approaches, the oil absorption is believed to be the most efficient method with simple operations, low cost and environmentally friendly. [9] However, traditional sorbents remain with several drawbacks due to the low absorption efficiency and capacity, limiting the practical application.…”

“…[9] However, traditional sorbents remain with several drawbacks due to the low absorption efficiency and capacity, limiting the practical application. [10] To overcome those issues, many porous sorbents were examined to deal with oil spill and chemical leakage, such as electrospun membrane, [6] nonwoven fabric, [7] aerogel [8] and composite. [11] Those sorbents show excellent hydrophobicity, high specific surface area (SSA) and high oil absorption capacity.…”