Gene expression profile in Liver, skeletal muscle, brown and white adipose tissues in mice after different interventions
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE70857 | GEO | 2015/07/14
SECONDARY ACCESSION(S): PRJNA289695
REPOSITORIES: GEO
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Project description:SIRT1 is a NAD+-dependent protein deacetylase. SIRT1 plays key roles in metabolic regulation and adaptation. In this study, we wanted to compare gene expression profile in SIRT1 overexpressing mice to WT mice submitted to different intervention (caloric restriction and exercise training) in different tissues (liver, skeletal muscle, brown and white adipose tissues). SIRT1 transgenic model has already been described (Pfluger et al., 2008). Here we used homozygote transgenic mice which had been backcrossed to C57Bl/6N background. 3 months old WT and SIRT1tg mice were fed with a low fat diet. After sacrifice, total mRNA obtained from brown adipose were used for microarray. Caloric restriction (CR) : everyother day feeding during 3 months Exercise training (EX) : mice were housed in running wheel cages during 10 weeks
2015-07-14 | E-GEOD-70857 | biostudies-arrayexpress
Project description:SIRT1 is a NAD+-dependent protein deacetylase. SIRT1 plays key roles in metabolic regulation and adaptation. In this study, we examined the difference of gene expression in brown adipose tissue from WT and SIRT1tg mice.
2014-10-15 | GSE62324 | GEO
Project description:SIRT1 is a NAD+-dependent protein deacetylase. SIRT1 plays key roles in metabolic regulation and adaptation. In this study, we examined the difference of gene expression in brown adipose tissue from WT and SIRT1tg mice. SIRT1 transgenic model (heterozygous transgenic model) has already been described (Pfluger et al., 2008). Here we used homozygote transgenic mice which had been backcrossed to C57Bl/6N background. 3 months old WT and SIRT1tg mice were fed with a low fat diet. After sacrifice, total mRNA obtained from brown adipose were used for microarray.
2014-10-15 | E-GEOD-62324 | biostudies-arrayexpress
Project description:Cockayne syndrome (CS) is an accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in the genes encoding the DNA repair proteins CSA or CSB. Csbm/m mice were given a high-fat, caloric-restricted or resveratrol-supplemented diet. The high-fat diet rescued the phenotype of Csbm/m mice at the metabolic, transcriptomic and behavioral levels. Additional analysis suggests that the premature aging seen in CS mice, nematodes and human cells results from aberrant PARP activation due to deficient DNA repair leading to decreased SIRT1 activity and mitochondrial dysfunction. Notably, β-hydroxybutyrate levels are increased by the high-fat diet; and β-hydroxybutyrate, PARP inhibition, or NAD+ supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB is able to displace activated PARP1 from damaged DNA to limit its activity. This study connects two emerging longevity metabolites, β-hydroxybutyrate and NAD+, through the deacetylase SIRT1 and suggests possible interventions for CS.
2014-12-22 | GSE62194 | GEO
Project description:NAD+ levels decline with age and in certain disease conditions. NAD+ precursors have been shown to stimulate NAD+ biosynthesis and ameliorate various age-associated diseases in mouse models. However, NAD+ metabolism is complicated in cancer and its role in triple-negative breast cancer (TNBC) remains elusive. Here, we show that NAD+ supplement suppresses tumor metastasis in a TNBC orthotopic patient-derived xenograft (PDX) model. Sirtuin1 lysine deacetylase (SIRT1) is required for the effects since SIRT1 knockdown blocks NAD+-suppressed tumor metastasis. Overexpression of SIRT1 effectively impairs the metastatic potential of TNBC. Importantly, the interaction between SIRT1 and p66Shc causes the deacetylation and functional inactivation of p66Shc, which inhibits epithelial-mesenchymal transition (EMT). Overall, we demonstrate that NAD+ supplementation executes its anti-tumor function via activating the SIRT1-p66Shc axis, which highlights the preventive and therapeutic potential of SIRT1 activators as effective interventions for TNBC.
2023-01-23 | GSE220683 | GEO
Project description:Chondrosarcomas represent the second most common primary bone malignancy. Despite the vulnerability of chondrosarcoma cells to nicotinamide adenine dinucleotide (NAD+) depletion, targeting the NAD+ synthesis pathway remains challenging due to broad implications in biological processes. Here, we establish SIRT1 as a central mediator reinforcing the dependency of chondrosarcoma cells on NAD+ metabolism via HIF-2α-mediated transcriptional reprogramming. SIRT1 knockdown abolishes aggressive phenotypes of chondrosarcomas in orthotopically transplanted tumors in mice. Chondrosarcoma cells thrive under glucose starvation by accumulating NAD+ and subsequently activating the SIRT1–HIF-2α axis. Decoupling this link via SIRT1 inhibition unleashes apoptosis and suppresses tumor progression in conjunction with chemotherapy. Unsupervised clustering analysis identifies a high-risk chondrosarcoma patient subgroup characterized by the upregulation of NAD+ biosynthesis genes. Finally, SIRT1 inhibition abolishes HIF-2α transcriptional activity and sensitizes chondrosarcoma cells to doxorubicin-induced cytotoxicity, irrespective of underlying pathways to accumulate intracellular NAD+. We provide system-level guidelines to develop therapeutic strategies for chondrosarcomas.
2023-12-01 | GSE248490 | GEO
Project description:In mammals, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1) constitute a nuclear NAD+ salvage pathway, regulating cellular functions of the NAD+-dependent deacetylase SIRT1. However, little is known about the molecular mechanisms by which NAD+ biosynthesis controls gene transcription in the nucleus. In this study, we show that stable knockdown of NAMPT or NMNAT-1 in MCF-7 breast cancer cells significantly reduced total cellular NAD+ levels. Expression microarray analyses demonstrate that both enzymes have broad and overlapping functions in gene regulation. SIRT1 is a key mediator of NAMPT- and NMNAT-1-dependent gene regulation, and is found at promoters of many of the target genes. Furthermore, SIRT1 deacetylase activity at these promoters is regulated by NAMPT and NMNAT-1. Most significantly, NMNAT-1 interacts with SIRT1 and is recruited to target gene promoters by SIRT1. Our results reveal an unexpected mechanism for the direct control of SIRT1 deacetylase activity at target gene promoters by NMNAT-1. Interactions between NMNAT-1 and SIRT1 at gene promoters may provide a platform for integration of multiple signaling pathways that regulate transcription. This SuperSeries is composed of the SubSeries listed below.
2009-05-28 | GSE13577 | GEO
Project description:The SIRT1 deacetylase is one of the best-studied potential mediators of some of the anti-aging effects of calorie restriction (CR); but its role in CR-dependent lifespan extension has not been demonstrated. We previously found that mice lacking both copies of SIRT1 displayed a shorter median lifespan than wild type mice on an ad libitum diet. Here we report that median lifespan extension in CR heterozygote SIRT1+/- mice was identical (51%) to that observed in wild type mice but SIRT1+/- mice displayed a higher frequency of some certain pathologies. Although larger studies in different genetic backgrounds are necessary , these results provide strong initial evidence for the requirement of SIRT1 for the anti-aging effects of CR, but suggest that its high expression is not required for CR-induced lifespan extension. Key words: SIRT1, caloric restriction, lifespan, anti-aging 2-5 month old male mice of 3 different genotypes (SIRT1+/+, SIRT1+/-, and SIRT1-/-) that had normal, reduced or no expression of SIRT1 were treated with either a 40% caloric restricted diet (CR) or an ad libitum diet (AL). 2-4 replicates of each experimental condition were used in the analysis.
2014-04-25 | E-GEOD-46895 | biostudies-arrayexpress
Project description:Attainment of a brown adipocyte cell phenotype in white adipocytes, with their abundant mitochondria and increased energy expenditure potential, is a legitimate strategy for combating obesity. The unique transcriptional regulators of the primary brown adipocyte phenotype are unknown, limiting our ability to promote brown adipogenesis over white. In the present work, we used microarray analysis strategies to study primary preadipocytes, and we made the striking discovery that brown preadipocytes demonstrate a myogenic transcriptional signature, whereas both brown and white primary preadipocytes demonstrate signatures distinct from those found in immortalized adipogenic models. We found a plausible SIRT1-related transcriptional signature during brown adipocyte differentiation that may contribute to silencing the myogenic signature. In contrast to brown preadipocytes or skeletal muscle cells, white preadipocytes express Tcf21, a transcription factor that has been shown to suppress myogenesis and nuclear receptor activity. In addition, we identified a number of developmental genes that are differentially expressed between brown and white preadipocytes and that have recently been implicated in human obesity. The interlinkage between the myocyte and the brown preadipocyte confirms the distinct origin for brown versus white adipose tissue and also represents a plausible explanation as to why brown adipocytes ultimately specialize in lipid catabolism rather than storage, much like oxidative skeletal muscle tissue. Keywords: In vitro differentiation
2007-05-31 | GSE7032 | GEO
Project description:SIRT1 is a nuclear NAD+-dependent protein deacetylase. Expression microarray analysis was used to study the effect of SIRT1 knockdown on gene expression in MCF-7 breast cancer cells.
2009-05-28 | GSE13459 | GEO