Nonionic Ethoxylated Surfactants Induce Adipogenesis in 3T3-L1 Cells

Recent studies have demonstrated that a number of environmental contaminants can act as metabolic disruptors and modulate metabolic function both in vitro and in vivo. 3T3-L1 mouse preadipocytes are commonly utilized to assess perturbations to adipogenesis, providing insight into environmental contaminants that may impact in vivo metabolic health. This study sought to assess whether various alkylphenol ethoxylates and alcohol ethoxylates (APEOs and AEOs, respectively), ubiquitous contaminants used in common household products, could disrupt metabolic health. 3T3-L1 cells were exposed to increasing concentrations of individual ethoxylated surfactants and base hydrophobes, and assessed for triglyceride accumulation (relative to a rosiglitazone-induced maximum response) and preadipocyte proliferation (relative to a differentiated vehicle control). We report herein that nonionic APEOs and AEOs promoted triglyceride accumulation and/or preadipocyte proliferation in 3T3-L1 cells at concentrations from 0.1 to 10 μM. Activity appeared to be an effect of the polyethoxylate chain length, as the alkylphenol/alcohol hydrophobes exhibited minimal or no adipogenic activity. In addition, nonylphenol ethoxylates (NPEO) of various ethoxylate chain lengths exhibited biphasic adipogenic activity, with increasing triglyceride accumulation and preadipocyte proliferation from NPEO (0, average ethoxylate number) through NPEO (4), and then decreasing activities from NPEO (4) through NPEO (20). Our results suggest potential metabolic impacts of these compounds at environmentally relevant concentrations, demonstrating a need to further assess molecular mechanisms and better characterize environmental concentrations of the specific AEOs and APEOs that are inducing the greatest degree of adipogenic activity herein.