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DNA methylation regulates hypothalamic gene expression linking parental diet during pregnancy to the offspring's risk of obesity in Psammomys obesus

Khurana, I., Kaspi, A., Ziemann, M., Block, T., Connor, T., Spolding, B., Cooper, A., Zimmet, P., El-Osta, A. and Walder, K. 2016, DNA methylation regulates hypothalamic gene expression linking parental diet during pregnancy to the offspring's risk of obesity in Psammomys obesus, International journal of obesity, vol. 40, no. 7, pp. 1079-1088, doi: 10.1038/ijo.2016.64.

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Title DNA methylation regulates hypothalamic gene expression linking parental diet during pregnancy to the offspring's risk of obesity in Psammomys obesus
Author(s) Khurana, I.
Kaspi, A.
Ziemann, M.
Block, T.
Connor, T.
Spolding, B.
Cooper, A.
Zimmet, P.
El-Osta, A.
Walder, K.
Journal name International journal of obesity
Volume number 40
Issue number 7
Start page 1079
End page 1088
Total pages 10
Publisher Nature Publishing Group
Place of publication London, Eng.
Publication date 2016-07
ISSN 1476-5497
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Nutrition & Dietetics
Summary BACKGROUND/OBJECTIVE: The rising incidence of obesity is a major public health issue worldwide. Recent human and animal studies suggest that parental diet can influence fetal development and is implicated with risk of obesity and type 2 diabetes in offspring. The hypothalamus is central to body energy homoeostasis and appetite by controlling endocrine signals. We hypothesise that offspring susceptibility to obesity is programmed in the hypothalamus in utero and mediated by changes to DNA methylation, which persist to adulthood. We investigated hypothalamic genome-wide DNA methylation in Psammomys obesus diet during pregnancy to the offspring's risk of obesity. METHODS: Using methyl-CpG binding domain capture and deep sequencing (MBD-seq), we examined the hypothalamus of offspring exposed to a low-fat diet and standard chow diet during the gestation and lactation period. RESULTS: Offspring exposed to a low-fat parental diet were more obese and had increased circulating insulin and glucose levels. Methylome profiling identified 1447 genomic regions of differential methylation between offspring of parents fed a low-fat diet compared with parents on standard chow diet. Pathway analysis shows novel DNA methylation changes of hypothalamic genes associated with neurological function, nutrient sensing, appetite and energy balance. Differential DNA methylation corresponded to changes in hypothalamic gene expression of Tas1r1 and Abcc8 in the offspring exposed to low-fat parental diet. CONCLUSION: Subject to parental low-fat diet, we observe DNA methylation changes of genes associated with obesity in offspring.
Language eng
DOI 10.1038/ijo.2016.64
Field of Research 111104 Public Nutrition Intervention
Socio Economic Objective 920411 Nutrition
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Macmillan Publishers
Persistent URL http://hdl.handle.net/10536/DRO/DU:30091852

Document type: Journal Article
Collection: School of Medicine
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