Details

Autor(en) / Beteiligte

• Kaspi, Antony
• Khurana, Ishant
• Ziemann, Mark
• Connor, Timothy
• Spolding, Briana
• Zimmet, Paul
• Walder, Ken
• El‐Osta, Assam

Titel

Diet during Pregnancy is Implicated in the Regulation of Hypothalamic RNA Methylation and Risk of Obesity in Offspring

Ist Teil von

• Molecular nutrition & food research, 2018-07, Vol.62 (14), p.e1800134-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2018

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Scope Early life nutrition has long‐lasting influence in adults through key mediators that modulate epigenetic states, although the determinants involved that underlie this response remain controversial. Because of the similarities between metabolic, physiological, and endocrine changes and those occurring in human type 2 diabetes, we studied the interaction of diet during pregnancy regulating RNA adenosine methylation (N6‐methyladenosine [m6A]) and the transcriptome in Psammomys obesus. Methods and results Breeding pairs were randomly allocated standard diet (total digestible energy 18 MJ kg−1) or low‐fat diet (15 MJ kg−1). Offspring were weaned onto the low‐fat diet at 4 weeks of age and given ad libitum access, resulting in two experimental groups: 1) male offspring of animals fed a low‐fat diet and weaned onto the low‐fat diet and 2) male offspring of animals fed a standard diet and weaned onto the low‐fat diet. Hypothalamic RNA was used to assess m6A by immunoprecipitation. Parental low‐fat diet alters the metabolic phenotype in offspring. An association between parental diet and hypothalamic m6A was observed in regulating the expression of FTO and METTL3 in the offspring. Conclusions We propose the regulatory capacity is now broadened for the first time to include m6A in developmental programming and obesity phenotype. A summary and hypothetical model illustrating that asymmetric DNA and RNA methylation serve precise epigenetic control over the expression of genes implicated in metabolic disease is provided. In this study, it is shown that parental nutrition is implicated in the control of hypothalamic m6A and the expression of an important obesity gene, CREBBP. The experimental results extend work previously done in the same model, showing that obesity genes have DNA methylation changes with parental diet.