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Wildtype Mouse Hypothalamus Cerebellum Fed Fast

ABSTRACT: The hypothalamus is a key site for the integration of the response to nutrient deprivation in higher organisms. Transcripts that are dynamically regulated in the hypothalamus by feeding and fasting are likely to play a regulatory role in energy balance. In order to identify hypothalamic genes whose expression is altered by fasting, we compared the transcriptomes of hypothalamic blocks from freely feeding vs overnight fasted mice using whole genome oligonucleotide arrays. In order to exclude changes due to non-specific neuronal stress responses to energy deprivation we simultaneously profiled the cerebellum, a brain site with no known regulatory role in energy balance. The power of this approach was illustrated by the fact that while we confirmed previous observations that the Sulfotransferase family 1A gene is upregulated by fasting in the hypothalamus, we showed that it was similarly upregulated in the cerebellum and is therefore unlikely to be specifically involved in the regulation of energy balance. In contrast, using three different methods of pathway enrichment analysis, multiple genes involved in mitochondrial oxidative phosphorylation were found to be co-ordinately downregulated by fasting in the hypothalamus but not in the cerebellum. These findings suggest that a switch from oxidative to non-oxidative metabolism in the hypothalamus may be an important element of the homeostatic response to nutrient deprivation. Keywords: hypothalamus, cerebellum, fasting, appetite, obesity

ORGANISM(S): Mus musculus

PROVIDER: GSE4221 | GEO | 2007/02/09

SECONDARY ACCESSION(S): PRJNA94863

REPOSITORIES: GEO

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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.

Project description:Background: Exposure to dichlorvos (DDVP), an organophosphorus pesticide, is known to result in neurotoxicity as well as other metabolic perturbations. However, the molecular causes of DDVP toxicity are poorly understood, especially in cells other than neurons and muscle cells. To obtain a better understanding of the process of non-neuronal DDVP toxicity, we exposed zebrafish to different concentrations of DDVP, and investigated the resulting changes in liver histology and gene transcription. Results: Functional enrichment analysis of genes affected by DDVP exposure identified a number of processes involved in energy utilization and stress response in the liver. The abundance of transcripts for proteins involved in glucose metabolism was profoundly affected, suggesting that carbon flux might be diverted toward the pentose phosphate pathway to compensate for elevated demand for energy and reducing equivalents for detoxification. Strikingly, many transcripts for molecules involved in Î²-oxidation and fatty acid synthesis were down-regulated. We found increases in message levels for molecules involved in reactive oxygen species responses as well as ubiquitination, proteasomal degradation, and autophagy. To ensure that the effects of DDVP on energy metabolism were not simply a consequence of poor feeding because of neuromuscular impairment, we fasted fish for 29 or 50 h and analyzed liver gene expression in them. The patterns of gene expression for energy metabolism in fasted and DDVP-exposed fish were markedly different.â Conclusion: We observed coordinated changes in the expression of a large number of genes involved in energy metabolism and responses to oxidative stress. These results argue that an appreciable part of the effect of DDVP is on energy metabolism and is regulated at the message level. Although we observed some evidence of neuromuscular impairment in exposed fish that may have resulted in reduced feeding, the alterations in gene expression in exposed fish cannot readily be explained by nutrient deprivation. Dichlorvos induced changes in gene expression in zebrafish were measured after 24 h exposures. A total of 20 arrays were processed with 4 replicates for each exposure condition (low, mid, and high) and 4 replicates for each of 2 control sets. Also, fasting induced changes in gene expression in zebrafish were measured after 24 hours fasting and 50 hours fasting. A total of 12 arrays were processed with 4 replicates for each exposure condition (no fasting, 24h fasting, 50h fasting).

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Wildtype Mouse Hypothalamus Cerebellum Fed Fast

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