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Impact of maternal high fat diet on hypothalamic transcriptome in neonatal Sprague Dawley rats

Maternal consumption of a high fat diet during early development has been shown to impact the formation of hypothalamic neurocircuitry, thereby contributing to imbalances in appetite and energy homeostasis and increasing the risk of obesity in subsequent generations. Early in postnatal life, the neu...

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Published in:PloS one 2017-12, Vol.12 (12), p.e0189492-e0189492
Main Authors: Barrand, Sanna, Crowley, Tamsyn M, Wood-Bradley, Ryan J, De Jong, Kirstie A, Armitage, James A
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description Maternal consumption of a high fat diet during early development has been shown to impact the formation of hypothalamic neurocircuitry, thereby contributing to imbalances in appetite and energy homeostasis and increasing the risk of obesity in subsequent generations. Early in postnatal life, the neuronal projections responsible for energy homeostasis develop in response to appetite-related peptides such as leptin. To date, no study characterises the genome-wide transcriptional changes that occur in response to exposure to high fat diet during this critical window. We explored the effects of maternal high fat diet consumption on hypothalamic gene expression in Sprague Dawley rat offspring at postnatal day 10. RNA-sequencing enabled discovery of differentially expressed genes between offspring of dams fed a high fat diet and offspring of control diet fed dams. Female high fat diet offspring displayed altered expression of 86 genes (adjusted P-value
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Male high fat diet offspring showed significant changes in collagen genes (Col1a1 and Col3a1) and significant upregulation of two genes involved in regulation of dopamine availability in the brain, tyrosine hydroxylase (Th) and dopamine reuptake transporter Slc6a3 (also known as Dat1). Transcriptional changes were accompanied by increased body weight, body fat and body length in the high fat diet offspring, as well as altered blood glucose and plasma leptin. 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Male high fat diet offspring showed significant changes in collagen genes (Col1a1 and Col3a1) and significant upregulation of two genes involved in regulation of dopamine availability in the brain, tyrosine hydroxylase (Th) and dopamine reuptake transporter Slc6a3 (also known as Dat1). Transcriptional changes were accompanied by increased body weight, body fat and body length in the high fat diet offspring, as well as altered blood glucose and plasma leptin. 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One</addtitle><date>2017-12-14</date><risdate>2017</risdate><volume>12</volume><issue>12</issue><spage>e0189492</spage><epage>e0189492</epage><pages>e0189492-e0189492</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Maternal consumption of a high fat diet during early development has been shown to impact the formation of hypothalamic neurocircuitry, thereby contributing to imbalances in appetite and energy homeostasis and increasing the risk of obesity in subsequent generations. Early in postnatal life, the neuronal projections responsible for energy homeostasis develop in response to appetite-related peptides such as leptin. To date, no study characterises the genome-wide transcriptional changes that occur in response to exposure to high fat diet during this critical window. We explored the effects of maternal high fat diet consumption on hypothalamic gene expression in Sprague Dawley rat offspring at postnatal day 10. RNA-sequencing enabled discovery of differentially expressed genes between offspring of dams fed a high fat diet and offspring of control diet fed dams. Female high fat diet offspring displayed altered expression of 86 genes (adjusted P-value&lt;0.05), including genes coding for proteins of the extra cellular matrix, particularly Collagen 1a1 (Col1a1), Col1a2, Col3a1, and the imprinted Insulin-like growth factor 2 (Igf2) gene. Male high fat diet offspring showed significant changes in collagen genes (Col1a1 and Col3a1) and significant upregulation of two genes involved in regulation of dopamine availability in the brain, tyrosine hydroxylase (Th) and dopamine reuptake transporter Slc6a3 (also known as Dat1). Transcriptional changes were accompanied by increased body weight, body fat and body length in the high fat diet offspring, as well as altered blood glucose and plasma leptin. Transcriptional changes identified in the hypothalamus of offspring of high fat diet mothers could alter neuronal projection formation during early development leading to abnormalities in the neuronal circuitry controlling appetite in later life, hence priming offspring to the development of obesity.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29240779</pmid><doi>10.1371/journal.pone.0189492</doi><tpages>e0189492</tpages><orcidid>https://orcid.org/0000-0001-5642-5196</orcidid><oa>free_for_read</oa></addata></record>
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subjects Abnormalities
Animals
Animals, Newborn
Appetite
Biology and Life Sciences
Blood glucose
Body fat
Body length
Body weight
Brain
Circuits
Coding
Collagen
Collagen (type I)
Dams
Diet
Diet, High-Fat
DNA methylation
Dopamine
Dopamine transporter
Energy balance
Female
Food
Gene expression
Gene regulation
Gene sequencing
Genes
Genomes
Health aspects
High fat diet
Homeostasis
Hydroxylase
Hypothalamus
Hypothalamus - metabolism
Insulin
Insulin-like growth factor II
Insulin-like growth factors
Laboratory rats
Leptin
Medicine
Medicine and Health Sciences
Neonates
Neural coding
Neurons
Neuropeptides
Neurosciences
Newborn babies
Nutrition
Obesity
Offspring
Peptides
Phenotype
Pregnancy
Priming
Proteins
Rats
Rats, Sprague-Dawley
Research and analysis methods
Ribonucleic acid
RNA
Rodents
Stem cells
Transcription
Transcriptome
Tyrosine
title Impact of maternal high fat diet on hypothalamic transcriptome in neonatal Sprague Dawley rats
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