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



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.



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.



Subject to parental low-fat diet, we observe DNA methylation changes of genes associated with obesity in offspring.
Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
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I
Khurana
Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
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Kaspi
Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
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M
Ziemann
Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
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T
Block
Metabolic Research Unit, Faculty of Health, Medicine, Nursing and Behavioural Sciences, Deakin University, Waurn Ponds, Victoria, Australia.
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T
Connor
Metabolic Research Unit, Faculty of Health, Medicine, Nursing and Behavioural Sciences, Deakin University, Waurn Ponds, Victoria, Australia.
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B
Spolding
Metabolic Research Unit, Faculty of Health, Medicine, Nursing and Behavioural Sciences, Deakin University, Waurn Ponds, Victoria, Australia.
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A
Cooper
Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
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P
Zimmet
Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.|Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.|Faculty of Medicine, Monash University, Melbourne, Victoria, Australia.
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A
El-Osta
Metabolic Research Unit, Faculty of Health, Medicine, Nursing and Behavioural Sciences, Deakin University, Waurn Ponds, Victoria, Australia.
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K
Walder
D000818:Animals; D019175:DNA Methylation / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2; D018752:Diet, Fat-Restricted; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development; D005786:Gene Expression Regulation; D005849:Gerbillinae; D007031:Hypothalamus / Q000378:metabolism*; D007774:Lactation; D039382:Maternal Nutritional Physiological Phenomena; D009765:Obesity / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*