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EC number: 284-366-9
CAS number: 84852-53-9
Effects of DBDPE exposure on body weight, liver weight, and
epididymis fat weight.
At 15 weeks, body weights of male mouse offspring in the DL group were
significantly higher than those in the VL group (P < 0.0001), whereas
there was no significant difference between the VL and DH group.
Compared with LFD groups, the liver weight was increased in HFD groups
significantly. However, no significant differences in liver weight were
observed between DBDPE-exposed and vehicle-exposed mice fed either a LFD
or HFD. The epididymis fat weight of mice in the DL group was
significantly higher than those in the VL group, and mice in the HFD
group had higher epididymis fat weight than LFD group.
Effect of DBDPE exposure on glucose homeostasis.
The effects of treatment with DBDPE or HFD on glucose homeostasis were
determined by GTT and ITT. Mice exposed to the HFD (VH and DH groups)
did not metabolize glucose as rapidly as control animals (VL group)
during the GTT, and exposed to DBDPE caused further slowing in glucose
metabolism. Similarly, glucose metabolism in VH and DH groups were
significant retarded compared with VL group after being injected with
insulin solution, without DBDPE effects.
Effect of DBDPE exposure on liver functions and injury.
We analyzed the levels of TG and TC in the liver and the results showed
that the levels of TG in the two groups fed with HFD increased
significantly, while the TC levels only increased significantly in group
DL. In addition, the liver function impairment was roughly assessed by
ALT and AST levels in serum. The results showed that the ALT level in
the DL group was significantly lower, but the other groups did not
change significantly. And the AST level were basically equivalent for
Effect of DBDPE exposure on metabolomics.
A representative 600 MHz 1H NMR spectra of the liver aqueous extracts
from mice was presented in Fig. S1. Chemical shift assignments for
metabolites were labelled in Fig. S1 and summarized in Table S2 of the
original publication. The 3D PCA score plot for all groups showed a
trend of separation of samples as a whole. The OPLS-DA score plots
showed that the groups can be clearly separated from each other. The
R2X, R2Y, Q2 and CV-ANOVA p-values were shown in Table 1 of the original
publication. The pairwise comparisons between four groups were used to
determine the effect of DBDPE, HFD and their joint actions on the
metabolic profile of mice (Wang et al., 2016). Based on the VIP values
obtained from the OPLS-DA model, combined with the FDR values, we
identified a total of 24 altered metabolites: bile acids, lipid,
leucine, isoleucine, valine, lactate, alanine, butyric acid, lysine,
acetate, glutamine, glutamate, glutathione, phosphocholine (PC),
uridine, glycerophosphocholine (GPC), dimethylallylpyrophosphate
(DMAPP), alpha-glucose, glycogen, thiamine, nicotinurate, inosine and
formate, which can be divided into amino acids, purines, lipids,
vitamins and other small molecules involved in energy metabolism. The
heatmap generated by the significantly changed metabolites is used to
represent the clustering between
different individual samples. In fact, both HFD and DBDPE caused
metabolomics changes, and combined exposure of HFD and DBDPE may enhance
the drug-induced metabolomics changes.
Specifically, compared with VL group, lactate, uridine, GPC, cyclic AMP,
nicotinurate and inosine were increased in all other groups while
thiamine, was lowered. In addition, bile acids, lipid, leucine,
isoleucine, valine, lysine, acetate and glutamine were reduced and
glutathione, PC and DMAPP were raised in VH group compared with VL
group. And, metabolites bile acids, lipid, butyric acid, glutamine,
glutamate, glutathione, PC, DMAPP and formate were increased, glycogen
was decreased after exposed to both DBDPE and HFD. In particular, after
exposure to DBDPE, although there were fewer metabolites that were
significantly changed in the LFD group, the trends were similar to those
in the joint exposure group. More detailed results of metabolite changes
between the groups are referenced in Table 2 of the original publication.
Effects of DBDPE exposure on the expression of some energy metabolism
In order to elucidate the mechanism of DBDPE-induced obesity, we
determined the expressions of genes involved in lipid and glucose
metabolism, which included fatty acid synthesis (SCD1, FASN, ACC,
SPEBP-1c), fatty acid uptake and lipid storage (PPARg, CD36),
b-oxidation (PPARa, Cpt1a), triglyceride synthesis
(DGAT1, DGAT2, Mogat1), triglyceride transport (Mttp), carbohydrate
metabolism (G6pase, Gck) and bile secretion (Shp, Fxr). After DBDPE or
HFD exposure, the expression of gene encoding the rate-limiting enzyme
SCD1 for biosynthesis of unsaturated fatty acids was significantly
reduced compared with VL group, and the DH group showed a more severe
trend. And, the gene expression of FASN was significant increased only
in the DH group compared with that in VL group. The gene expression of
ACC was significant decreased in both VH and DH groups. There was no
significant change in the gene expression of SPEBP-1c and Cpt1a.
Compared with VL, the gene expression of PPARg in DL group and VH group
were increased, and the increase caused by HFD is more significant. The
mRNA levels of CD36
and PPARa were significant increase in VH group compared with VL group.
As for DGAT1 and DGAT2, encoding the enzyme involved in de novo
synthesis of triglyceride, showed no significant change in all groups.
And, the expression of Mogat1, a key enzyme in triglyceride synthesis,
had an increasing trend in the DL and VH groups and the DH group showed
a more severe trend compared with VL group. The expression of microsomal
triglyceride transfer protein Mttp had the similar changes to DGAT2. As
glucose metabolism related genes, the expression of G6pase and Gck had
different trends. The mRNA levels of G6pase was significant decreased in
VH while the Gck was decreased in DL group. And Shp, compared with
expression in the VL group, showed significant decreased in all other
groups, while Fxr had significant increase in DL and VH groups.
In this study, the authors explored potential DBDPE toxic effects on
male mouse offspring after perinatal exposure. During the perinatal
period, pregnant ICR mice were exposed to DBDPE (0.1 mg/kg body weight)
via oral gavage. After weaning, male offspring were fed on a low-fat
diet and a high-fat diet, respectively. The authors measured and
recorded body weight, liver weight, and epididymis fat mass, blood
biochemical markers, metabolites changes in liver, and gene expression
involved in lipid and glucose homeostasis. The authors report that
perinatal exposure to DBDPE increased the risk of obesity in mouse
offspring and affected triglyceride synthesis, bile secretion, purine
synthesis, mitochondrial function and glucose metabolism; furthermore,
the use of high-fat feeding may further exacerbate these effects. The
authors then claim that their results show that early-life exposure to
low doses of DBDPE may promote the development of metabolic dysfunction,
which in turn can induce obesity. However the relevanc eof this protocol
and the background variability of the parmeters remain unknown and the
findings are of limited relevance for human health risk assessment.
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