Di-(2-Ethylhexyl)-Phthalate (DEHP) Causes Impaired Adipocyte Function and Alters Serum Metabolites
Nora Klöting PLOS ONE December 2015
Di-(2-ethylhexyl)-phthalate (DEHP), an ubiquitous environmental contaminant, has been
shown to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological
studies, but the underlying mechanisms are still unknown.
We therefore tested the hypothesis that chronic DEHP exposure causes impaired insulin sensitivity, affects body
weight, adipose tissue (AT) function and circulating metabolic parameters of obesity resistant
129S6 mice in vivo. An obesity-resistant mouse model was chosen to reduce a potential
obesity bias of DEHP effects on metabolic parameters and AT function. The metabolic
effects of 10-weeks exposure to DEHP were tested by insulin tolerance tests and quantitative
assessment of 183 metabolites in mice. Furthermore, 3T3-L1 cells were cultured with
DEHP for two days, differentiated into mature adipocytes in which the effects on insulin
stimulated glucose and palmitate uptake, lipid content as well as on mRNA/protein expression
of key adipocyte genes were investigated.
We observed in female mice that DEHP treatment causes enhanced weight gain, fat mass, impaired insulin tolerance, changes in
circulating adiponectin and adipose tissue Pparg, adiponectin and estrogen expression.
Serum metabolomics indicated a general increase in phospholipid and carnitine concentrations.
In vitro, DEHP treatment increases the proliferation rate and alters glucose uptake in
adipocytes.
Taken together, DEHP has significant effects on adipose tissue (AT) function
and alters specific serum metabolites. Although, DEHP treatment led to significantly
impaired insulin tolerance, it did not affect glucose tolerance, HOMA-IR, fasting glucose,
insulin or triglyceride serum concentrations. This may suggest that DEHP treatment does
not cause impaired glucose metabolism at the whole body level.