In vitro and in vivo evidence of bioenergetic metabolism alteration by mono-(2-ethylhexyl) phthalate
To better understand the potential alteration of muscle bioenergetic metabolism by the obesogenic toxicant mono-(2ethylhexyl) phthalate (MEHP) the objectives of this research were to determine the: 1) association between urinary MEHP levels and plasma fatty acid levels in women with obesity who participated in National Health and Nutrition Examination Survey (NHANES) studies, and 2) in vitro effects of MEHP on fatty acid, or glucose supported mitochondrial energetics in C2C12 muscle cells.
... muscle cells. Results: The association between urinary MEHP from NHANES participants with plasma fatty acid levels was studied via secondary data statistical analyses. 14 C-palmitic acid oxidation, Seahorse fatty acid oxidation and glycolysis stress tests and western blot analyses were conducted on C2C12 cells exposed to increasing MEHP concentrations. Increased urinary MEHP in women with obesity was associated with increased plasma gamma-linolenic and arachidonic acid levels. C2C12 myotubes exposed to increasing MEHP concentrations, displayed decreased fatty acid oxidation and mitochondrial bioenergetics. Acyl-CoA synthetase long chain 5 (ACSL5) protein level was also upregulated with increasing MEHP exposure in C2C12 myoblasts. Glycolysis was not significantly modified with increased exposure of C2C12 cells to MEHP. Conclusions: MEHP exposure may alter fatty acid utilization at the whole-body level in women with obesity and fatty acid utilization in muscle cells. Our findings are consistent with the idea that women with obesity may be particularly susceptible to the effects of MEHP, which alters fatty acid metabolism in muscle cells. Background Obesogens are defined as chemical compounds that contribute to impaired lipid metabolism, dysregulation of adipogenesis, and consequently, may contribute to the development of obesity (1). One of these obesogens, di(2-ethylhexyl) phthalate (DEHP), is one of the primary phthalate plasticizers used in North America, and is commonly found in food packaging and medical devices (2,3). DEHP is non-covalently bound into matrices and therefore can leach into the human body and be metabolised via lipases into the monoester derivative mono-(2ethyl hexyl) phthalate (MEHP), one