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

Antony Kaspi; Ishant Khurana; Mark Ziemann; Timothy Connor; Briana Spolding; Paul Zimmet; Ken Walder; Assam El-Osta
Abstract
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.Breeding pairs were randomly allocated standard diet (total digestible energy 18 MJ kg ) or low-fat diet (15 MJ kg ). 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.-1We propose the regulatory capacity is now broadened for the first time to include m6A in developmental programming and obesity phenotype.
Journal MOLECULAR NUTRITION & FOOD RESEARCH
ISSN 1613-4133
Published 07 Jun 2018
Volume
Issue
Pages e1800134
DOI 10.1002/mnfr.201800134
Type Journal Article
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