Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression in adipose tissue of intrauterine growth restricted (IUGR) and Macrosomic animals that developed in a crowded uterine horn

ABSTRACT: Animals that are growth restricted in utero may show rapid postnatal growth that ultimately results in adult obesity. Macrosomic animals at birth typically remain large and are also obese as adults. Our goal was to examine the differences between animals that reach obesity in different ways. We also aimed to examine gene expression in animals that start out lean and stay lean compared to those that start out lean and become fat. We used microarrays to detail gene expression in adipose tissue. 3 samples each from IUGR animals with rapid postnatal growth (IH), IUGR animals with slower postnatal growth (IL), and macromsomic animals (M).

ORGANISM(S): Mus musculus

SUBMITTER: Julia Taylor

PROVIDER: E-GEOD-33761 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Though obesity is a global epidemic, the physiological mechanisms involved are little understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesized that maternal diet influences fetal 5-HT exposure, which then influences central appetite network development and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant low protein fed rat mothers exhibited elevated serum 5-HT, which was also evident in the placenta and fetal brains at E16.5. This increase was associated with reduced hypothalamic expression of 5-HT2CR - the primary 5-HT receptor influencing appetite. As expected, reduced 5-HT2CR expression was associated with impaired sensitivity to 5-HT-mediated appetite suppression. 5-HT primarily achieves effects on appetite via 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We reveal that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC and that 5-HT2AR mRNA is increased in the hypothalamus of in utero growth restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals are more sensitive to 5-HT2AR agonist-induced appetite suppression. These findings may not only reveal a 5-HT-mediated mechanism underlying programming of obesity susceptibility but also provide a promising means to correct it, via a 5-HT2AR agonist treatment. The study was carried out using male Wistar rats (Rattus norvegicus). On postnatal day 3, two experimental groups of offspring were established: controls (offspring of control dams) and recuperated (offspring of dams fed a low-protein diet (8% protein, w/v), but nursed by control dams. The animals were fed with standard chow until 3 months of age where the brains were collected for transcriptomic profiling

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Gene expression in adipose tissue of intrauterine growth restricted (IUGR) and Macrosomic animals that developed in a crowded uterine horn

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