Perinatal exposure to di-(2-ethylhexyl) phthalate induces hepatic lipid accumulation mediated by diacylglycerol acyltransferase 1.
Hum Exp Toxicol
; 40(10): 1698-1709, 2021 Oct.
Article
em En
| MEDLINE
| ID: mdl-33832334
ABSTRACT
INTRODUCTION:
Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer in consumer products and medical devices. It is also suspected to exacerbate the development of fatty liver. However, the mechanisms underlying excessive lipid synthesis and its deposition in the liver are yet to be identified. This study was aimed to evaluate the molecular mechanisms of hepatic lipid accumulation in adult male offspring after perinatal exposure to DEHP.METHOD:
Corn oil and DEHP (0.75 mg/kg/day) were administered once per day to dam from gestation day 6 to postnatal day (PND) 21 by oral gavage. After the weaning period, DEHP treated male pups were categorized into early life stage- and lifelong period group. Male rats both control and early life stage group administered corn oil, and lifelong period group administered DEHP from PND 22 to 70. Histological examination and triglyceride (TG) levels in the liver were analyzed. Expressions of transcription factors associated with lipid accumulation in the liver were analyzed.RESULTS:
Both early life stage- and lifelong period group, hepatic TG levels, and mRNA and protein expression of diacylglycerol acyltransferase 1 (DGAT1) were significantly higher than control (TG all p < 0.05, mRNA & protein p < 0.05 and p < 0.001, respectively). The average body weight from PND 35 to 63, and mRNA and protein expression of sterol regulatory element binding protein 1c in lifelong period group were significantly lower than control (all p < 0.05); however, alanine transaminase were significantly higher than control (p < 0.01).CONCLUSION:
Perinatal exposure to DEHP may induce the hepatic lipid accumulation through up-regulation of DGAT1 expression.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dietilexilftalato
/
Hepatopatia Gordurosa não Alcoólica
/
Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article