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Environ Res. 2015 Jul;140:145-56. doi: 10.1016/j.envres.2015.03.036. Epub 2015 Apr 9.

Cyclohexane-1,2-dicarboxylic acid diisononyl ester and metabolite effects on rat epididymal stromal vascular fraction differentiation of adipose tissue.

Author information

1
Research Institute of the McGill University Health Centre, Canada; Department of Medicine, McGill University, Montréal, Québec, Canada.
2
Research Institute of the McGill University Health Centre, Canada.
3
Synthèse AptoChem Inc., Montréal, Québec, Canada.
4
Research Institute of the McGill University Health Centre, Canada; Department of Medicine, McGill University, Montréal, Québec, Canada; Department of Biochemistry, McGill University, Montréal, Québec, Canada; Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada. Electronic address: vassilios.papadopoulos@mcgill.ca.

Erratum in

  • Environ Res. 2016 Jan;144(Pt A):170-1.

Abstract

Plastics are generally mixed with additives like plasticizers to enhance their flexibility, pliability, and elasticity proprieties. Plasticizers are easily released into the environment and are absorbed mainly through ingestion, dermal contact, and inhalation. One of the main classes of plasticizers, phthalates, has been associated with endocrine and reproductive diseases. In 2002, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) was introduced in the market for use in plastic materials and articles intended to come into contact with food, and it received final approval from the European Food Safety Authority in 2006. At present, there is limited knowledge about the safety and potential metabolic and endocrine-disrupting properties of DINCH and its metabolites. The purpose of this study was to evaluate the biological effects of DINCH and its active metabolites, cyclohexane-1,2-dicarboxylic acid (CHDA) and cyclohexane-1,2-dicarboxylic acid mono isononyl ester (MINCH), on rat primary stromal vascular fraction (SVF) of adipose tissue. DINCH and its metabolite, CHDA, were not able to directly affect SVF differentiation. However, exposure of SVF to 50 μM and 100 μM concentrations of MINCH affected the expression of Cebpa and Fabp4, thus inducing SVF preadipocytes to accumulate lipids and fully differentiate into mature adipocytes. The effect of MINCH was blocked by the specific peroxisome proliferator-activated receptor (PPAR)-α antagonist, GW6471. Taken together, these results suggest that MINCH is a potent PPAR-α agonist and a metabolic disruptor, capable of inducing SVF preadipocyte differentiation, that may interfere with the endocrine system in mammals.

KEYWORDS:

Adipocyte; CHDA; DINCH; Differentiation; MINCH; PPAR; Phthalates

PMID:
25863588
DOI:
10.1016/j.envres.2015.03.036
[Indexed for MEDLINE]

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