Mono(2-ethylhexyl)phthalate accumulation disturbs energy metabolism of fat cells

Abstract

Phthalates are lipophilic and tend to accumulate in adipose tissue, an important regulator of energy balance and glucose homeostasis. The study aimed to determine whether cellular phthalate accumulation influenced fat cell energy metabolism. Following a 3-day treatment with adipogenesis-inducing medium and a 2-day treatment with adipogenesis-maintaining medium, 3T3-L1 cells differentiated into adipocytes in the presence of a phthalate at a clinically relevant concentration (30-300 μM) for another 6 days. Two phthalates, di(2-ethylhexyl)phthalate and di-n-butylphthalate, and their metabolites, mono(2-ethylhexyl)phthalate (MEHP) and mono-n-butylphthalate, were used here. The phthalate treatments caused no marked effect on cytotoxicity and adipogenesis. Only the MEHP-treated adipocytes were found having smaller lipid droplets; MEHP accumulated in cells in a dose- and time-dependent manner. The MEHP-treated adipocytes exhibited significant increases in lipolysis and glucose uptake; quantitative real-time polymerase chain reaction (qPCR) analysis revealed correlated changes in expression of marker genes involved in adipogenesis, lipid metabolism, and glucose uptake. Analysis of oxygen consumption rate (a mitochondrial respiration indicator) and extracellular acidification rate (a glycolysis indicator) indicated a higher energy metabolism in the adipocytes. qPCR analysis of critical genes involved in mitochondrial biogenesis and/or energy metabolism showed that expression of peroxisome proliferator-activated receptor γ coactivator-1α, sirtuin 3, and protein kinase A were significantly enhanced in the MEHP-treated adipocytes. In vitro evidence of MEHP impacts on lipolysis, glucose uptake/glycolysis, and mitochondrial respiration/biogenesis demonstrates that MEHP accumulation disturbs energy metabolism of fat cells.

Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood pressure, adiposity, cholesterol metabolism and social interaction in mouse offspring

“…DEHP was recently reported to be a ligand for activation of PPARs and thus might be implicated in adiposity induced by DEHP (Latini et al 2006;Viana Abranches et al 2011). DEHP disrupts the metabolism of fatty acids in adipocytes and thereby promotes their differentiation, ultimately leading to obesity (Desvergne et al 2009;Hao et al 2012;Chiang et al 2015). However, how maternal DEHP exposure induces adiposity in offspring and whether a PPAR-dependent mechanism is involved in this process in our in vivo system remain for further investigation.…”

The Effects of Endocrine Disruptors on Adipogenesis and Osteogenesis in Mesenchymal Stem Cells: A Review

“…Thus, PPARγ and SREBF-1 are key transcriptional factors in adipogenesis. The expression of C/EBPα and expression of factors promoted by PPARγ, such as lipoprotein lipase and fatty acid binding protein 4/adipocyte protein 2 (aP2), have been shown to be increased in response to DDT, DDE, 4-NP, BPA, PCB-77, DEHP, MEHP, and BBP (37, 39, 42, 45, 46, 66, 68, 69, 73, 75, 76, 78, 82–84, 86–89). p , p ′-DDT has also been shown to increase binding of C/EBPα to its DNA response element, demonstrating that the promotion of adipogenesis may be occurring through both increased expression and activation of targeted receptors (66).…”

Characterization of air freshener emission: the potential health effects

“…Repeated exposure causes damage to the nerves, and irritates the eyes and skin. Thus, using a spray air freshener for long periods should be avoided (Chiang et al, 2014;Hao et al, 2012).…”