Whole Transcriptome Analysis of Hypothalamus in Mice during Short-Term Starvation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE289833 | GEO | 2025/02/23
REPOSITORIES: GEO
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Project description:Systemic acute inflammatory signals can cause profound anorexia by disrupting the physiological appetite regulation in the hypothalamic milieu. Conversely, obesity related chronic inflammation of the hypothalamus can disturb anorexigenic signals and promote abnormal body weight control. The aim of the present study was to compare the global hypothalamic endophenotype in C57/Bl6 mice exposed to a high-fat diet or with acute illness mediated by LPS. Ten-week old male C57/Bl6 mice (n=18) were randomly divided into four groups; the control 1 group (n =3) was fed a normal diet whereas the high-fat diet (HFD) group (n =6) was fed a high-fat diet for eight weeks. The control 2 group (n=3) received an intraperitoneal injection of saline whereas the LPS group (n=6) received an intraperitoneal injection of LPS. Mice were sacrificed 18-hr post-injection. Both control 2 and LPS groups were fed a normal diet for eight weeks before the injection. The hypothalamic regions were removed and analysed using a 2D LC-MS methodology. The proteomic analysis profiled 9,235 proteins (q<0.05) across all biological states, of which 522 proteins were found modulated in the HFD group and another 579 in the LPS group. The proteomic profiles demonstrated that the systemic acute inflammation linked with anorexia induced a negative feedback loop of appetite control in the hypothalamus, suggesting an effort to re-establish homeostasis. By contrast, the chronic inflammation associated with obesity initiated a “perpetual cycle” of positive feedback enhancement of appetite regulation further exacerbating positive energy balance.
2018-01-29 | PXD002119 | Pride
Project description:Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore studying the changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. We show that hypothalamic expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Targeting these systems seems a promising strategy to avoid the development of cancer-induced eating disorders. C26-colon adenocarcinoma cells were subcutaneously inoculated in CDF1 mice. After 20 days, hypothalami were dissected and subjected to gene expression profiling. The total dataset consists of 2 parts; dataset 1, a pilot stuy in which mice were injected with increasing number of tumour cells and pooled samples were arrayed; and dataset 2, the main study in which mice were injected with 1 million tumour cells and samples were individually arrayed.
2013-11-14 | E-GEOD-44080 | biostudies-arrayexpress
Project description:Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore studying the changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. We show that hypothalamic expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Targeting these systems seems a promising strategy to avoid the development of cancer-induced eating disorders. C26-colon adenocarcinoma cells were subcutaneously inoculated in CDF1 mice. After 20 days, hypothalami were dissected and subjected to gene expression profiling. The total dataset consists of 2 parts; dataset 1, a pilot stuy in which mice were injected with increasing number of tumour cells and pooled samples were arrayed; and dataset 2, the main study in which mice were injected with 1 million tumour cells and samples were individually arrayed.
2013-11-14 | E-GEOD-44081 | biostudies-arrayexpress
Project description: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
2007-02-09 | GSE4221 | GEO
Project description:Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore studying the changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. We show that hypothalamic expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Targeting these systems seems a promising strategy to avoid the development of cancer-induced eating disorders.
2013-11-14 | GSE44081 | GEO
Project description:Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore studying the changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. We show that hypothalamic expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Targeting these systems seems a promising strategy to avoid the development of cancer-induced eating disorders.
2013-11-14 | GSE44080 | GEO
Project description:Sodium appetite is an instinct that involves avid specific intention. It is elicited by sodium deficiency, stress-evoked ACTH and by reproduction. Genome-wide microarrays in sodium deficient mice, or following ACTH infusion, showed upregulation of hypothalamic genes, including DARPP-32, dopamine receptors-1 and -2, alpha-2C-adrenoceptor, and STEP. Both DARPP-32 and neural plasticity regulator, ARC were upregulated in lateral hypothalamic orexinergic neurons by sodium deficiency. Administration of dopamine D1- (SCH23390) and D2-receptor (raclopride) antagonists reduced gratification of sodium appetite triggered by sodium deficiency. SCH23390 was specific, having no effect on osmotic-induced water drinking, whereas raclopride also reduced water intake. D1-receptor knockout mice had normal sodium appetite, indicating compensatory regulation. It was insensitive to SCH23390, confirming the absence of off-target effects. Bilateral microinjection of SCH23390 (100nM in 200nL) into rats? lateral hypothalamus greatly reduced sodium appetite. Gene Set Enrichment Analysis in hypothalami of mice with sodium appetite showed significant enrichment of gene sets previously linked to addiction (opiates, cocaine). This finding of concerted gene regulation was attenuated upon gratification with perplexingly rapid kinetics of only 10 minutes, anteceding significant absorption of salt from the gut. Salt appetite and hedonic liking of salt taste have evolved over more than a hundred million years e.g. being present in Metatheria. Drugs causing pleasure and addiction are comparatively recent and likely reflect usurping of evolutionary ancient systems with high survival value by the gratification of contemporary hedonic indulgences. Our findings outline a novel molecular logic for instinctive behavior encoded by the brain with possible important translational-medical implications. Transcripts were profiled in the hypothalamus and whole brain of control and salt craving animals to determine the gene expression profile corresponding to that behavioral state. We show an over-representation of addiction-related genes in the set that is common to different methods of salt craving. Mouse hypothalamus and whole brain under three conditions: control, furosemide treated, and ACTH treated. 4 or 5 biological replicated per group. Two channels - experimental and reference are used.
2011-07-04 | E-GEOD-29451 | biostudies-arrayexpress
Project description:Appetite is largely controlled by hypothalamic neurons. Variation near the Negr1 gene has been significantly associated with increased body mass in multiple human genome-wide association studies. Accordingly, we ablated Negr1 in the hypothalamus of mice and demonstrated this was sufficient to generate a metabolic phenotype. To investigate the molecular mechanisms through which Negr1 influences feeding behaviour, we performed paired-end RNAseq on the Illumina platform in hypothalamic tissue from Negr1 knockout and control mice This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2015-11-11 | E-ERAD-404 | biostudies-arrayexpress
Project description:Brain-derived serotonin favors appetite in mice following its binding to the Htr1a and Htr2b receptors in arcuate neurons of the hypothalamus. In this study, we identified that CREB is the transcriptional effector of brain-derived serotonin control of appetite in arcuate nuclei. In this dataset, we identified the downstream genes of CREB in arcuate neurons of the hypothalamus controling appetite. We isolated hypothalami of wild type and Creb-pomcCre-/- (deleted for Creb selectively in arcuate neurons of the hypothalamus) mice and performed microarray experiments.
2010-12-14 | E-GEOD-26037 | biostudies-arrayexpress
Project description:We performed gene expression microarray analysis of the hypothalamic response to starvation in neonatal wild-type mice, and in Snord116del mice that are a mouse model for PWS. This study is motivated by the neonatal feeding problems observed in several genetic diseases including Prader-Willi syndrome (PWS). Later in life, individuals with PWS develop hyperphagia and obesity due to lack of appetite control. We hypothesize that failure to thrive in infancy and later-onset hyperphagia may be related and could be due to a defect in the hypothalamus. In this study, we performed gene expression microarray analysis of the hypothalamic response to starvation in neonatal wild-type mice, and in Snord116del mice that are a mouse model for PWS. The neonatal starvation response was dramatically different from that reported in adult rodents. Genes that are affected by adult starvation are not changed in the hypothalamus of 5 day-old pups that were starved for 6 hrs. Unlike in adult rodents, expression levels of Nanos2 and Pdk4 were increased, and those of Pgpep1, Ndph, Brms1l, Mett10d, and Snx1 were decreased after fasting. In addition, we compared hypothalamic gene expression profiles at days 5 and 13 to document developmental changes. Notably, the gene expression profiles of Snord116del deletion mice and wild-type littermates were very similar at both postnatal days 5 and 13, and after starvation. We compared hypothalamic RNA between Snord116del mice with wild type (C57BL/6J) littermates at P5 and P13, with or without fasting treatment. We are particularly interested in the following comparisons: Comparison 1: wild type vs. PWS deletion in P5 non-starved mice; Comparison 2: wild type vs. PWS deletion in P5 fasting mice; Comparison 3: non-starved vs. fasting in P5 wild type mice; Comparison 4: non-starved vs. fasting in P5 PWS deletion mice; Comparison 5: wild type vs. PWD deletion in P13 non-starved mice; Comparison 6: P5 wild type vs. P13 wild type mice;
2010-02-28 | E-GEOD-14984 | biostudies-arrayexpress