White adipose tissue browning in the R6/2 mouse model of Huntington's disease
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE79711 | GEO | 2016/07/28
SECONDARY ACCESSION(S): PRJNA316818
REPOSITORIES: GEO
Similar Datasets
Project description:We investigated gene expression signatures in subcutaneous inguinal adipose tissue obtained from wild type and R6/2 mice with the aim to identify gene expression changes and signalling pathway alterations in adipose tissue relevant to HD. Gene expression was assessed using Affymetrix GeneChip® Mouse Gene 2.0 ST Array. Target genes were technically validated using real-time quantitative PCR. 12 subcutaneous inguinal white adipose tissue samples were analyzed by affymetrix: 6 wild-type samples; 6 R6/2 mouse samples.
2016-07-28 | E-GEOD-79711 | biostudies-arrayexpress
Project description:We investigated gene expression signatures in subcutaneous adipose tissue obtained from control subjects, premanifest HD gene carriers and manifest HD subjects with the aim to identify gene expression changes and signalling pathway alterations in adipose tissue relevant to HD. Gene expression was assessed using Affymetrix GeneChip® Human Gene 1.0 ST Array. Target genes were technically validated using real-time quantitative PCR and the expression signature was validated in an independent subject cohort.
2016-03-20 | GSE73655 | GEO
Project description:Huntington's disease (HD) is a fatal, autosomal dominantly inherited neurodegenerative disorder, characterised not only by progressive cognitive, motor and psychiatric impairments, but also of peripheral pathology. In both human HD and in mouse models of HD there is evidence of increased energy expenditure and weight loss, alongside altered body composition. Unlike white adipose tissue (WAT), brown adipose tissue (BAT), as well as brown-like cells within WAT, expresses the mitochondrial protein, uncoupling protein 1 (UCP1). UCP1 enables dissociation of cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Hyperplasia of brown/beige cells in WAT has been suggested to enhance energy expenditure. In this study, we therefore investigated the gene expression profile, histological appearance, response to cold challenge and functional aspects of WAT in the R6/2 HD mouse model and selected WAT gene expression in the full-length Q175 mouse model of HD. WAT from R6/2 mice contained significantly more brown-like adipocyte regions and had a gene profile suggestive of the presence of brown-like adipocytes, such as higher Ucp1 expression. Cold exposure induced Ucp1 expression in R6/2 inguinal WAT to a markedly higher degree as compared to the thermogenic response in WT WAT. Alongside this, gene expression of transcription factors (Zfp516 and Pparα), important inducers of WAT browning, were increased in R6/2 inguinal WAT, and Creb1 was highlighted as a key transcription factor in HD. In addition to increased WAT Ucp1 expression, a trend towards increased mitochondrial oxygen consumption due to enhanced uncoupling activity was found in inguinal R6/2 WAT. Key gene expressional changes (increased expression of (Zfp516 and Pparα)) were replicated in inguinal WAT obtained from Q175 mice. In summary, for the first time, we here show that HD mouse WAT undergoes a process of browning, resulting in molecular and functional alterations that may contribute to the weight loss and altered metabolism observed with disease progression.
| S-EPMC4972251 | biostudies-literature
Project description:Huntington’s disease is a genetic disease caused by a single mutation. It is characterised by progressive movement, emotional and cognitive deficits. R6/2 transgenic mice carrying the Huntington’s disease mutation have a progressive neurological phenotype, including deterioration in cognitive function. The mechanism underlying the cognitive deficits in R6/2 mice is unknown, but dysregulated gene expression, reduced neurotransmitter levels and abnormal synaptic function are present before the cognitive decline becomes pronounced. Our goal here was to ameliorate the cognitive phenotype in R6/2 mice using a combination drug therapy (tacrine, moclobemide and creatine) aimed boosting neurotransmitter levels in the brain. Treatment from 5 weeks of age prevented deterioration in two different cognitive tasks until at least 12 weeks. However, motor deterioration continued unabated. Microarray analysis of global gene expression revealed that many genes significantly up- or down-regulated in untreated R6/2 mice had returned towards normal levels after treatment. Thus dysregulated gene expression was reversed by the combination treatment in the R6/2 mice and probably underlies the observed improvements in cognitive function. Our study shows that cognitive decline caused by a genetic mutation can be slowed by a combination drug treatment, and gives hope that cognitive symptoms in HD can be treated. Keywords = HD Keywords = Huntingtin Keywords = cognitive disorder Keywords = R6/2 Keywords = transgenic mice Keywords = gene expression Keywords = microarray Keywords: ordered
2004-06-01 | GSE857 | GEO
Project description:A challenge in treating Huntington's disease (HD) is the complexity of affected brain regions and cell types. We carried out a systematic analysis of cell type-specific changes in cortex and striatum from R6/2 mice at 8 and 12w, and discovered major expression changes in oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs), suggesting that many OLs were arrested in an immature state. Causal gene network analysis implicates PRKCE and SWI/SNF in abnormal OL maturation. PRKCE protein was dramatically decreased. Disrupted cell-to-cell signaling between medium spinyneurons and OL that may contribute to neuronal dysfunction was identified in R6/2 mice using ligand-receptor analysis. These findings reveal novel insights into OL pathology, span multiple brain regions in humans and mice and suggest therapeutic strategies.
2022-11-14 | GSE180294 | GEO
Project description:The adipose tissue is a key site regulating energy metabolism. One of the contributing factors behind this is browning of white adipose tissue (WAT), however, knowledge of the intracellular determinants of browning process remains incomplete. By generating adipocyte-specific Senp2 knockout (Senp2-aKO) mice, here we showed that SENP2 negatively regulates browning by de-conjugating SUMO from C/EBPβ. Senp2-aKO mice were resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and heat production. Senp2 knockout promoted beige adipocyte accumulation in inguinal WAT by upregulation of thermogenic gene expression. In addition, SENP2 knockdown promoted thermogenic adipocyte differentiation of precursor cells isolated from inguinal and epididymal WATs. Mechanistically, sumoylated C/EBPβ, a target of SENP2, suppressed expression of HOXC10, a browning inhibitor, by recruiting a transcriptional repressor DAXX. These findings indicate that a SENP2-C/EBPβ-HOXC10 axis operates for the control of beige adipogenesis in inguinal WAT.
2023-11-27 | GSE189387 | GEO
Project description:The adipose tissue is a key site regulating energy metabolism. One of the contributing factors behind this is browning of white adipose tissue (WAT), however, knowledge of the intracellular determinants of browning process remains incomplete. By generating adipocyte-specific Senp2 knockout (Senp2-aKO) mice, here we showed that SENP2 negatively regulates browning by de-conjugating SUMO from C/EBPβ. Senp2-aKO mice were resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and heat production. Senp2 knockout promoted beige adipocyte accumulation in inguinal WAT by upregulation of thermogenic gene expression. In addition, SENP2 knockdown promoted thermogenic adipocyte differentiation of precursor cells isolated from inguinal and epididymal WATs. Mechanistically, sumoylated C/EBPβ, a target of SENP2, suppressed expression of HOXC10, a browning inhibitor, by recruiting a transcriptional repressor DAXX. These findings indicate that a SENP2-C/EBPβ-HOXC10 axis operates for the control of beige adipogenesis in inguinal WAT.
2023-11-27 | GSE189326 | GEO
Project description:Gene expression profiling of striatum in R6/2 Huntington’s disease (HD) model mouse. Striatum gene set contained gene expression alterations in other neuronal populations, such as oligodendrocyte, astrocyte, microglia and interneuron.
2020-06-03 | GSE113929 | GEO
Project description:Differentiation of brown adipocytes is a crucial process for adaptive thermogenesis, which is stimulated by various factors. We found robust browning of inguinal white adipose tissue in UCP1/ApoE-DKO mice, but not in ApoE-KO mice, under high-fat diet condition. We used microarray to determine the genes specifically regulated in the browning white adipose tissue in UCP1/ApoE-DKO mice.
2018-10-01 | GSE95273 | GEO
Project description:Gene expression profiling of purified medium spiny neurons (MSNs) in R6/2 Huntington’s disease (HD) model mouse. To purify MSNs by FACS, R6/2 was crossed with Scn4b-Venus transgenic mouse expressing Venus in MSNs. MSN gene set excluded gene expression alterations in other neuronal populations, indicating the gene set displays MSN-specific pathological changes in HD. We identified the dysregulated genes expression, which are associated with apoptosis and transcriptional regulation, and found considerable number of disease causative genes in MSN gene set.
2020-06-03 | GSE113928 | GEO