Intrauterine exposure to low-dose DBP in the mice induces obesity in offspring via suppression of UCP1 mediated ER stress.
Animals
Apoptosis
/ drug effects
Body Composition
/ drug effects
Dibutyl Phthalate
/ administration & dosage
Endocrine Disruptors
/ administration & dosage
Endoplasmic Reticulum Stress
/ drug effects
Energy Metabolism
/ drug effects
Female
Mice
Obesity
/ chemically induced
Pregnancy
Prenatal Exposure Delayed Effects
/ chemically induced
Uncoupling Protein 1
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
06
02
2020
accepted:
17
09
2020
entrez:
2
10
2020
pubmed:
3
10
2020
medline:
2
1
2021
Statut:
epublish
Résumé
Dibutyl phthalate (DBP) is recognized as an environmental endocrine disruptor that has been detected in fetal and postnatal samples. Recent evidence found that in utero DBP exposure was associated with an increase of adipose tissue weight and serum lipids in offspring, but the precise mechanism is unknown. Here we aimed to study the effects of in utero DBP exposure on obesity in offspring and examine possible mechanisms. SPF C57BL/6J pregnant mice were gavaged with either DBP (5 mg /kg/day) or corn oil, from gestational day 12 until postnatal day 7. After the offspring were weaned, the mice were fed a standard diet for 21 weeks, and in the last 2 weeks 20 mice were selected for TUDCA treatment. Intrauterine exposure to low-dose DBP promoted obesity in offspring, with evidence of glucose and lipid metabolic disorders and a decreased metabolic rate. Compared to controls, the DBP exposed mice had lower expression of UCP1 and significantly higher expression of Bip and Chop, known markers of endoplasmic reticulum (ER) stress. However, TUDCA treatment of DBP exposed mice returned these parameters nearly to the levels of the controls, with increased expression of UCP1, lower expression of Bip and Chop and ameliorated obesity. Intrauterine exposure of mice to low-dose DBP appears to promote obesity in offspring by inhibiting UCP1 via ER stress, a process that was largely reversed by treatment with TUDCA.
Identifiants
pubmed: 33004990
doi: 10.1038/s41598-020-73477-3
pii: 10.1038/s41598-020-73477-3
pmc: PMC7529907
doi:
Substances chimiques
Endocrine Disruptors
0
Uncoupling Protein 1
0
Dibutyl Phthalate
2286E5R2KE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16360Références
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