Transcriptomics

Dataset Information

36

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats


ABSTRACT: 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

ORGANISM(S): Rattus norvegicus  

SUBMITTER: Sue O'zanne  Giles S Yeo   Malgorzata Martin   Brian Yee Hong Lam   Brian Y Lam    

PROVIDER: E-GEOD-76012 | ArrayExpress | 2016-02-26

SECONDARY ACCESSION(S): GSE76012PRJNA305996

REPOSITORIES: GEO, ArrayExpress

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Although obesity is a global epidemic, the physiological mechanisms involved are not well 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 an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT i  ...[more]

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