PMID- 29240779 OWN - NLM STAT- MEDLINE DCOM- 20180116 LR - 20240327 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 12 DP - 2017 TI - Impact of maternal high fat diet on hypothalamic transcriptome in neonatal Sprague Dawley rats. PG - e0189492 LID - 10.1371/journal.pone.0189492 [doi] LID - e0189492 AB - 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<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. FAU - Barrand, Sanna AU - Barrand S AUID- ORCID: 0000-0001-5642-5196 AD - Faculty of Health, School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia. FAU - Crowley, Tamsyn M AU - Crowley TM AD - Faculty of Health, School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia. AD - MMR, BCRG, School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia. FAU - Wood-Bradley, Ryan J AU - Wood-Bradley RJ AD - Faculty of Health, School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia. FAU - De Jong, Kirstie A AU - De Jong KA AD - Faculty of Health, School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia. FAU - Armitage, James A AU - Armitage JA AD - Faculty of Health, School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia. LA - eng PT - Journal Article DEP - 20171214 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM MH - Animals MH - *Animals, Newborn MH - *Diet, High-Fat MH - Female MH - Hypothalamus/*metabolism MH - Phenotype MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley MH - *Transcriptome PMC - PMC5730210 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/12/15 06:00 MHDA- 2018/01/18 06:00 PMCR- 2017/12/14 CRDT- 2017/12/15 06:00 PHST- 2017/06/07 00:00 [received] PHST- 2017/11/27 00:00 [accepted] PHST- 2017/12/15 06:00 [entrez] PHST- 2017/12/15 06:00 [pubmed] PHST- 2018/01/18 06:00 [medline] PHST- 2017/12/14 00:00 [pmc-release] AID - PONE-D-17-21729 [pii] AID - 10.1371/journal.pone.0189492 [doi] PST - epublish SO - PLoS One. 2017 Dec 14;12(12):e0189492. doi: 10.1371/journal.pone.0189492. eCollection 2017.