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Genome-wide analysis of transcription factor FoxO1-responsive gene expression in the ventromedial hypothalamus

ABSTRACT: Analysis of gene expression regulated by FoxO1 in the ventromedial hypothalamus (VMH) of wildtype and knockout mice. Results provide important information of gene expression in the VMH. The transcription factor FoxO1 contributes to leptin and insulin action, including cells in the brain. However, the neurons mediating these effects and the identity of the molecular targets through which FoxO1 exerts metabolic actions remains to be defined.

ORGANISM(S): Mus musculus

PROVIDER: GSE36948 | GEO | 2012/03/31

SECONDARY ACCESSION(S): PRJNA157341

REPOSITORIES: GEO

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Genome-wide analysis of transcription factor FoxO1-responsive gene expression in the ventromedial hypothalamus

Project description:Analysis of gene expression regulated by FoxO1 in the ventromedial hypothalamus (VMH) of wildtype and knockout mice. Results provide important information of gene expression in the VMH. The transcription factor FoxO1 contributes to leptin and insulin action, including cells in the brain. However, the neurons mediating these effects and the identity of the molecular targets through which FoxO1 exerts metabolic actions remains to be defined. For the gene expression profiling, total RNA was obtained from the VMH of WT and VMH-specific FoxO1 KO mice using Qiagen RNeasy Lipid Tissue Mini Kit (Qiagen Sciences, Maryland) and Phase Lock Gel (5 Prime Inc., Gaithersburg, MD). To make sure reproducibility and biological significance, triple hybridizations were performed for each genotype with the RNA from three independent VMH samples, each sample contains RNA from three animals (biological replicates). Genomics and Microarray Core Facility at UT-Southwestern (http://microarray.swmed.edu/) checked RNA quality with Bioanalyzer Chip and processed the samples for hybridization with Illumina Mouse-6 V2 BeadChip (Illumina Inc., San Diego, CA). We used Partek Genomics Suite 6.5 (Partek Inc., St Louis, MO) and Ingenuity Pathway Analysis (Ingenuity Systems, Inc., Redwood City, CA) for data analysis.

2012-03-30 | E-GEOD-36948 | biostudies-arrayexpress

Single nucleus RNA-seq atlas of mouse ventromedial hypothalamus

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Single nucleus RNA-seq atlas of macaque ventromedial and dorsomedial hypothalamus

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Transcriptional profiling of microdissected ventromedial hypothalamus in Nkx2-1 f/f vs. Nkx2-1 f/f; Sf1Cre female mice

Project description:Microdissected ventromedial hypothalamus (VMH) was profiled to identify transcriptional changes after Nkx2-1 ablation in female mice. Total RNA was extracted from conditional mutants (Nkx2-1 f/f; Sf1Cre) and floxed controls (Nkx2-1 f/f) at postnatal day 10 (P10) and profiled using Mouse ref8 v2.0 Illumina chips and reagents (n=4/group). The tissue profiled is microdissected ventromedial hypothalamus from P10 female mice. Controls and mutants are analyzed in quadruplicate.

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Expression of ventromedial hypothalamus (VMH) from electroconvulsive seizure (ECS) treated C57Bl/6 mice

Project description:The ventromedial nucleus of the hypothalamus (VMH) is thought to a satiety center and a potential target for anti-obesity therapy. Electroconvulsive seizure (ECS) therapy is highly effective in psychiatric diseases including depression, but also implicated beneficial effects on other neurological diseases. Although it has been reported that the neurons in the VMH are strongly activated by ECS stimulation, the effect of ECS in this hypothalamic subnucleus remains unknown. To address this issue, we investigated molecular changes in the VMH in response to ECS by utilizing a method of laser-capture microdissection coupled with microarray analysis, and examined behavioral effects of ECS via VMH activation. ECS significantly induced gene expression not only immediate-early genes such as Fos, Fosb and Jun, but also Bdnf, Adcyap1, and Hrh1 in the VMH after a single or repeated stimulus. Mice received one or 7 times shock of ECS and their brains were collected at 2 h (VMH_1stECS2h, VMH_7thECS2h) or 6 h after shock (VMH_1stECS6h, VMH_7thECS6h). The brains of sham-treated animals were collected at 2 h after treatment(VMH_sham). The VMH was microdissected from dehydrated brain sections, and its total RNA was extracted. RNA samples from two or three animals were pooled to minimize the impact of biological variance. After nucleotide amplification by the ovation amplification, the gene expression profiles were obtained by the Affymetrix microarray analysis. The microarray analysis was performed twice using different sets of animals.

2012-05-29 | E-GEOD-38311 | biostudies-arrayexpress

Expression of ventromedial hypothalamus (VMH) from electroconvulsive seizure (ECS) treated C57Bl/6 mice

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Astrocytic circadian clock control of energy expenditure by transcriptional stress responses in the ventromedial hypothalamus

Project description:Mice carrying a mutation which deletes Bmal1 in Gfap-expressing astrocytes, and control animals were fed either a standard diet or a high fat diet for 16 weeks. Conditional deletion of Bmal1 in Gfap cells decreased weight gain and increased energy expenditure under high fat diet, hence the transcriptome of Brown Adipose Tissue (BAT) and Ventromedial Hypothalamus (VMH) were obtained.

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Thyroid hormone receptor beta in the ventromedial hypothalamus is essential for the physiological regulation of food intake and body weight

Project description:The obesity epidemic is a significant global health issue. Improved understanding of the mechanisms which regulate appetite and body weight will provide the rationale for the design of novel anti-obesity therapies. Thyroid hormones play a key role in metabolic homeostasis through their interaction with thyroid hormone receptors (TR) which function as ligand inducible transcription factors. The TR beta isoform (TRβ) is expressed in the ventromedial hypothalamus (VMH), a brain area important for control of energy homeostasis. Here we report that selective knock down of TRβ in the VMH of adult mice results in severe obesity due to hyperphagia and reduced energy expenditure. The observed increase in body weight is of a similar magnitude to murine models of the most extreme forms of monogenic obesity. These data identify TRβ in the VMH as a major physiological regulator of food intake and energy homeostasis.

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