RNA-seq of hypothalamus from Zrsr1 WT and Zrsr1 mutant mice.
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500
ORGANISM(S): Mus musculus
SUBMITTER: Alfonso Gutiérrez Adán
PROVIDER: E-MTAB-8012 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Nutrient deficiency during perinatal development is associated with an increased risk to develop obesity, diabetes and hypertension in adulthood. However, the molecular mechanisms underlying the developmental programming of the metabolic syndrome remain largely unknown. Given the essential role of the hypothalamus in the integration of nutritional, endocrine and neuronal cues, here we have analyzed the profile of the hypothalamus transcriptome in 180-day-old rats born to dams fed either a control (200 g/kg) or a low-protein (80 g/kg) diet throughout pregnancy and lactation. From a total of 26,209 examined genes, 688 were up-regulated and 309 down-regulated (P<0.003) by early protein restriction. Based on the hypothesis that variations in gene expression levels often reflect changes in gene’s activity and that transcriptional networks are at the heart of physiological functions, we identified two gene clusters regulating common cellular processes whose expression is coordinately regulated by perinatal protein restriction. The first one is constituted by several genes of the insulin signaling pathway which, additionally, act as gatekeeper genes for regulation of nutrient sensing. The second cluster encompasses a functional network of nuclear receptors and co-regulators of transcription involved in the detection and use of lipid nutrients as fuel which, in addition, link temporal and nutritional cues to metabolism through their tight interaction with the circadian clock. Collectively, these results indicate that the programming of the hypothalamic circuits regulating energy homeostasis is a key step in the development of obesity associated with malnutrition in early life and provide a valuable starting point for the direct and systematic experimental analysis of the role of the hypothalamus in the physiopathological disturbances associated with the programming of the metabolic syndrome. Five rats fed a control diet, and five rats fed a low-protein diet. All rats are male.
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2010-05-18 | E-GEOD-18970 | biostudies-arrayexpress
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Project description:Background: Negative energy balance (NEB) is an imbalance between energy intake and energy requirements for lactation and body maintenance, affecting high-yielding dairy cows after calving and is of considerable economic importance due to its negative impact on fertility and health in dairy herds. The hypothalamus is central to the neural control of homeostasis. It is anticipated that the cow hypothalamus experience extensive biochemical changes during the early post partum period in an effort to re-establish metabolic homeostasis. There is variation in the tolerance to NEB between individual cows. In order to understand the genomic regulation of ovulation in hypothalamic tissue during NEB transcriptional patterns between tolerant and sensitive animals was examined. A short term dietary restriction heifer model was developed which induced abrupt onset of anoestrus in some animals (Restricted Anovulatory; RA) while others maintained oestrous cyclicity (Restricted Ovulatory; RO). In addition a third control group (C) received a higher level of normal feeding. Heifers were slaughtered and hypothalamic tissue was collected after 18 days of differential feeding. mRNAseq was performed to examine differential gene expression profiles in hypothalamic tissue between groups. Results: A total of 15,295 genes were expressed in hypothalamic tissue. The largest difference between groups was observed in the comparison between RA and RO heifers, with 1094 genes shown to be significantly differentially expressed (SDE). Innatedb pathway analysis showed that these SDE genes were associated with 6 canonical pathways (P < 0.01), of which neuroactive ligand-receptor interaction was the most significant. Within the comparisons the main over-represented pathway functions appear to be immune response including neuroprotection (CXCL10, Q1KLR3, IFIH1, IL1 and IL8; RA v C and RA v RO); energy homeostasis (AgRP and NPY; RA v RO); cell motility (CADH1, DSP and TSP4; RO v C) and prevention of GnRH release (NTSR1 IL1?, IL1?, NPY and PACA; RA v RO). Conclusion: This information assists in understanding the genomic factors regulating the influence of diet restriction on fertility and may assist in to optimise nutritional and management systems that improve reproductive performance. A short term dietary restriction heifer model was developed which induced abrupt onset of anoestrus in some animals (Restricted Anovulatory; RA) while others maintained oestrous cyclicity (Restricted Ovulatory; RO). In addition a third control group (C) received a higher level of normal feeding. Heifers were slaughtered and hypothalamic tissue was collected after 18 days of differential feeding. mRNAseq was performed to examine differential gene expression profiles in hypothalamic tissue between groups.
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