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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

LanguageEnglish
Article number1800134
JournalMolecular Nutrition and Food Research
Volume62
Issue number14
DOIs
Publication statusPublished - 1 Jul 2018

Keywords

  • Psammomys obesus
  • RNA methylation
  • animal model(s)
  • gene-environment interactions
  • hypothalamus
  • obesity

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

Cite this

Kaspi, Antony ; Khurana, Ishant ; Ziemann, Mark ; Connor, Timothy ; Spolding, Briana ; Zimmet, Paul ; Walder, Ken ; El-Osta, Assam. / Diet during Pregnancy is Implicated in the Regulation of Hypothalamic RNA Methylation and Risk of Obesity in Offspring. In: Molecular Nutrition and Food Research. 2018 ; Vol. 62, No. 14.
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abstract = "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.",
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Kaspi, A, Khurana, I, Ziemann, M, Connor, T, Spolding, B, Zimmet, P, Walder, K & El-Osta, A 2018, 'Diet during Pregnancy is Implicated in the Regulation of Hypothalamic RNA Methylation and Risk of Obesity in Offspring', Molecular Nutrition and Food Research, vol. 62, no. 14, 1800134. https://doi.org/10.1002/mnfr.201800134

Diet during Pregnancy is Implicated in the Regulation of Hypothalamic RNA Methylation and Risk of Obesity in Offspring. / Kaspi, Antony; Khurana, Ishant; Ziemann, Mark; Connor, Timothy; Spolding, Briana; Zimmet, Paul; Walder, Ken; El-Osta, Assam.

In: Molecular Nutrition and Food Research, Vol. 62, No. 14, 1800134, 01.07.2018.

Research output: Contribution to journalArticle

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AU - Kaspi, Antony

AU - Khurana, Ishant

AU - Ziemann, Mark

AU - Connor, Timothy

AU - Spolding, Briana

AU - Zimmet, Paul

AU - Walder, Ken

AU - El-Osta, Assam

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