Perinatal phthalate and high-fat diet exposure induce sex-specific changes in adipocyte size and DNA methylation

Autor: Hong Chen, Aleksandra Gorski, Laura Moody, Isabel Digan, Yuan Xiang Pan, Daniel G. Kougias, Janice M. Juraska, Aaron Hong, Paul M. Jung
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Offspring
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Phthalic Acids
Adipose tissue
010501 environmental sciences
Biology
Diet
High-Fat
01 natural sciences
Biochemistry
Article
03 medical and health sciences
chemistry.chemical_compound
Sex Factors
Pregnancy
Internal medicine
Lactation
Adipocyte
Adipocytes
medicine
Animals
Rats
Long-Evans
Molecular Biology
Cell Size
0105 earth and related environmental sciences
Lipoprotein lipase
Adipogenesis
Nutrition and Dietetics
Triglyceride
Body Weight
Phthalate
DNA Methylation
Frizzled Receptors
Receptors
Neurotransmitter
Lipoprotein Lipase
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Animals
Newborn
Gene Expression Regulation
chemistry
Prenatal Exposure Delayed Effects
DNA methylation
Body Composition
Female
Zdroj: The Journal of Nutritional Biochemistry. 65:15-25
ISSN: 0955-2863
DOI: 10.1016/j.jnutbio.2018.11.005
Popis: Environmental factors such as diet and endocrine-disrupting chemicals have individually been shown to mediate metabolic function. However, the underlying mechanism by which the combination disrupts adipocyte morphology and fat storage remains unknown. The current study evaluated early-life programming by diet and phthalate exposure. During gestation and lactation, pregnant Long-Evans hooded rat dams were fed either a control (C) or high-fat (HF) diet and were orally administered one of three phthalate dosages (0, 200 or 1000 μg/kg/day), yielding six groups of offspring: C-0, C-200, C-1000, HF-0, HF-200 and HF-1000. On postnatal day (PND) 90, gonadal fat pads were collected and analyzed for histology, gene expression and DNA methylation. Differences in body weight were observed only in males. Hematoxylin and eosin staining revealed larger adipocyte size in HF-0 vs. C-0 females. Exposure to 200 or 1000 μg/kg/day phthalates modulated diet-induced changes in adipose morphology. Compared to C-0 females, HF-0 females also had higher expression of the adipogenesis gene Wnt receptor, frizzled 1 (Fzd1) and the triglyceride cleaving enzyme lipoprotein lipase (Lpl). These increases in gene expression were accompanied by lower DNA methylation surrounding the transcription start sites of the two genes. Diet-driven effects were observed in unexposed females but not in phthalate-treated rats. Results suggest a sex-specific association between perinatal HF diet and body weight, adipocyte size and DNA methylation. Perinatal phthalate exposure appears to produce a phenotype that more closely resembles HF-fed animals.
Databáze: OpenAIRE
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