Publication Date
9-30-2022
Journal
Science Advances
DOI
10.1126/sciadv.abo3991
PMID
36170368
PMCID
PMC9519050
PubMedCentral® Posted Date
9-28-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Arcuate Nucleus of Hypothalamus, Body Mass Index, Epigenesis, Genetic, Epigenomics, Female, Genome-Wide Association Study, Humans, Hypothalamus, Male, Mice, Obesity
Abstract
Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and occurs in genomic regions enriched for heritability of body mass index in humans. Our results offer a potential explanation for both the limited ontogenic windows for and sex differences in sensitivity to developmental programming of obesity and provide a rich resource for epigenetic analyses of developmental programming of energy balance.
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