Gene expression profile from short-term caloric restriction in mouse adipose tissue
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE60596 | GEO | 2015/12/31
SECONDARY ACCESSION(S): PRJNA258631
REPOSITORIES: GEO
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Project description:To provide a robust understanding of a transcriptomic change by short-term CR at body fat of mice, we applied three serial strengths of CR to mice including 15%, 30%, and 45% reduction of carbon source. Using Affymetrix mouse 1.0 ST array platform, we obtained and analyzed the transcriptome data for significantly changed genes in expression. Here, we identified 446 genes and categorized the genes based on their biological roles. We observed gradual down-regulation of several signaling pathways including insulin/insulin-like growth factor (IGF) 1, epidermal growth factor (EGF), transforming growth factor beta (TGF-β) and canonical Wingless-type mouse mammary tumor virus integration site (Wnt) signaling according to the CR strengths. Many genes related to structural feature including extracellular matrix (ECM), cell adhesion and cytoskeleton were also down-regulated with a strong correlation to the serial CR treatments. Furthermore, genes for cell cycle and adipogenesis were down-regulated. According to previous studies, these are target functions of the aforementioned four signaling pathways. On the other hand, the genes for specific metabolic features including tricarboxylic acid (TCA) cycle and electron transport chain (ETC) exhibited a transcriptional increase. In addition, adipose tissue expansion markers such as leptin, Mesoderm specific transcript (Mest) and Secreted frizzled-related sequence protein 5 (Sfrp5), and most genes for transport and immune response showed a down-regulation by CR. Comparing gene expression profiles to understand transcriptomic changes of adipose tissue by serial strength (15%, 30%, and 45%) of short-term (10 weeks) caloric restriction to young age (18 weeks) mice (n=3 in each group).
2015-12-31 | E-GEOD-60596 | biostudies-arrayexpress
Project description:Caloric restriction (CR) is one of the most robust interventions shown to delay aging in diverse species, including rhesus monkeys (Macaca mulatta). Identification of factors involved in CR brings a promise of translatability to human health and aging. Here, we show that CR induced a profound change in abundance of circulating microRNAs (miRNAs) linked to growth and insulin signaling pathway, suggesting that miRNAs are involved in CR’s mechanisms of action in primates. Deep sequencing of plasma RNA extracts enriched for short species revealed a total of 243 unique species of miRNAs including 47 novel species. Approxi- mately 70% of the plasma miRNAs detected were conserved between rhesus monkeys and humans. CR induced or repressed 24 known and 10 novel miRNA species. Regression analysis revealed correlations between bodyweight, adiposity, and insulin sensitivity for 10 of the CR-regulated known miRNAs. Sequence alignment and target identification for these 10 miRNAs identify a role in signaling downstream of the insulin receptor. The highly abundant miR-125a-5p correlated positively with adiposity and negatively with insulin sensitivity and was negatively regulated by CR. Putative target pathways of CR- associated miRNAs were highly enriched for growth and insulin signaling that have previously been implicated in delayed aging. Clustering analysis further pointed to CR-induced miRNA regula- tion of ribosomal, mitochondrial, and spliceosomal pathways. These data are consistent with a model where CR recruits miRNA- based homeostatic mechanisms to coordinate a program of delayed aging.
2017-08-04 | GSE102242 | GEO
Project description:This study explored the role of the growth hormone (GH) / insulin-like growth factor 1 (IGF-1) axis on the life-long caloric restriction (CR)-associated remodeling of white adipose tissue (WAT). Adipocyte size and gene expression profiles, using high-density oligonucleotide microarrays, were analyzed in WAT of six- to seven-month old wild Wistar rats fed ad libitum (AL) or subjected to a 30% caloric restriction (CR), and heterozygous transgenic dwarf rats bearing an anti-sense GH transgene fed ad libitum (Tg). While not significant in Tg rats, adipocyte size was significantly reduced in CR rats compared with AL rats. The microarray data based on the principal component analysis demonstrated that the gene expression profile of CR rats markedly differed from the AL rats, while Tg hardly differed, suggesting that CR-associated WAT remodeling was predominantly regulated in a GH/IGF-1-independent manner. The gene cluster with the largest change induced by CR included several genes involved in lipid biosynthesis and inflammation. Moreover, many of the genes transcriptionally regulated by sterol regulatory element binding proteins (SREBPs) were found in the cluster related to lipid biosynthesis. Real-time reverse transcription polymerase chain reaction analysis confirmed that the expression of SREBP-1 and its down-stream targets was particularly up-regulated in CR rats compared with SREBP-2 and its down-stream targets. Our findings suggest that SREBP-1 is a major transcription factor in CR-associated remodeling of WAT, and might be one of the key regulators of the anti-aging and pro-longevity effects of CR. The three groups: GH antisense, caloric restriction, and the control were compared by using PCA.
2012-09-27 | E-GEOD-30668 | biostudies-arrayexpress
Project description:This study explored the role of the growth hormone (GH) / insulin-like growth factor 1 (IGF-1) axis on the life-long caloric restriction (CR)-associated remodeling of white adipose tissue (WAT). Adipocyte size and gene expression profiles, using high-density oligonucleotide microarrays, were analyzed in WAT of six- to seven-month old wild Wistar rats fed ad libitum (AL) or subjected to a 30% caloric restriction (CR), and heterozygous transgenic dwarf rats bearing an anti-sense GH transgene fed ad libitum (Tg). While not significant in Tg rats, adipocyte size was significantly reduced in CR rats compared with AL rats. The microarray data based on the principal component analysis demonstrated that the gene expression profile of CR rats markedly differed from the AL rats, while Tg hardly differed, suggesting that CR-associated WAT remodeling was predominantly regulated in a GH/IGF-1-independent manner. The gene cluster with the largest change induced by CR included several genes involved in lipid biosynthesis and inflammation. Moreover, many of the genes transcriptionally regulated by sterol regulatory element binding proteins (SREBPs) were found in the cluster related to lipid biosynthesis. Real-time reverse transcription polymerase chain reaction analysis confirmed that the expression of SREBP-1 and its down-stream targets was particularly up-regulated in CR rats compared with SREBP-2 and its down-stream targets. Our findings suggest that SREBP-1 is a major transcription factor in CR-associated remodeling of WAT, and might be one of the key regulators of the anti-aging and pro-longevity effects of CR.
2012-09-27 | GSE30668 | GEO
Project description:To characterize gene expression that is dependent on the strength of calorie restriction (CR), we obtained transcriptome at different levels of glucose, which is a major energy and carbon source for budding yeast. To faithfully mimic mammalian CR in yeast culture, we reconstituted and grew seeding yeast cells in fresh 2% YPD media before inoculating into 2%, 1%, 0.5% and 0.25% YPD media to reflect different CR strengths. We collected and characterized 160 genes that responded to CR strength based on the rigorous statistical analyses of multiple test corrected ANOVA (adjusted é value < 0.1 or raw é value < 0.0031) and Pearson correlation (|r| > 0.7). Based on the individual gene studies and the GO Term Finder analysis of 160 genes, we found that CR dosedependently and gradually increased mitochondrial function at the transcriptional level. Therefore, we suggest these 160 genes are markers that respond to CR strength and that might be useful in elucidating CR mechanisms, especially how stronger CR extends life span more.
2008-10-02 | GSE9217 | GEO
Project description:To characterize gene expression that is dependent on the strength of calorie restriction (CR), we obtained transcriptome at different levels of glucose, which is a major energy and carbon source for budding yeast. To faithfully mimic mammalian CR in yeast culture, we reconstituted and grew seeding yeast cells in fresh 2% YPD media before inoculating into 2%, 1%, 0.5% and 0.25% YPD media to reflect different CR strengths. We collected and characterized 160 genes that responded to CR strength based on the rigorous statistical analyses of multiple test corrected ANOVA (adjusted é value < 0.1 or raw é value < 0.0031) and Pearson correlation (|r| > 0.7). Based on the individual gene studies and the GO Term Finder analysis of 160 genes, we found that CR dosedependently and gradually increased mitochondrial function at the transcriptional level. Therefore, we suggest these 160 genes are markers that respond to CR strength and that might be useful in elucidating CR mechanisms, especially how stronger CR extends life span more. Experiment Overall Design: Different glucose levels: 2%, 1%, 0.5%, and 0.25% Experiment Overall Design: Three biological replicates in each level
2008-10-26 | E-GEOD-9217 | biostudies-arrayexpress
Project description:The complexity of the plant cell walls creates many challenges for microbial decomposition. Clostridium phytofermentans, an anaerobic bacterium isolated from forest soil, directly breaks down and utilizes many plant cell wall carbohydrates. The objective of this research is to understand constraints on rates of plant decomposition by C. phytofermentans and identify molecular mechanisms that may overcome these limitations. Experimental evolution via repeated serial transfers during exponential growth was used to select for C. phytofermentans genotypes that grow more rapidly on cellobiose, cellulose and xylan. To identify the underlying mutations an average of 13,600,000 paired-end 100bp paired end reads were generated per population resulting in ~300 fold coverage of each site in the genome. A mixture of alleles fixed in the population down to frequencies of 5% could be identified with statistical confidence. Many mutations are in carbohydrate-related genes including the promoter regions of glycoside hydrolases and amino acid substitutions in ABC transport proteins involved in carbohydrate uptake, signal transduction sensors that detect specific carbohydrates, proteins that affect the export of extracellular enzymes, and regulators of unknown specificity. Protein structural modeling of the ABC transporter complex proteins suggests that mutations in these genes may alter the recognition of carbohydrates by substrate-binding proteins and communication between the intercellular face of the transmembrane proteins and the ATPase binding protein. Experimental evolution was effective in identifying molecular constraints on the rate of cellulose and hemicellulose fermentation and selected for putative gain of function mutations that do not typically appear in traditional molecular genetic screens. The results reveal new strategies for evolving and engineering microorganisms for faster growth on plant carbohydrates. Experimental evolution via repeated serial transfers during exponential growth was used to select for C. phytofermentans genotypes that grow more rapidly on cellobiose. Microarray analysis was performed on 1 time point from the evolved lines and the initial founder
2013-11-20 | E-GEOD-52494 | biostudies-arrayexpress
Project description:Calorie restriction (CR) and exercise training (EX) are two critical lifestyles for the prevention and treatment of metabolic diseases, such as obesity and diabetes. Brown adipose tissue (BAT) and skeletal muscle (SkM) are two important organs to generate heat. Here we provide detailed transcriptional profiling of these two thermogenic tissues from mice treated with CR and/or EX. We demonstrate the transcriptional reprogramming of BAT and SkM according to CR, but little to EX. Consistent with this, CR induces genes encoding adipokines or myokines alteration in BAT and SkM, respectively. Deconvolution analysis implies differences of subpopulations of myogenic cells, mesothelial cells and endogenic cells in BAT, and demonstrates differences of subpopulations of satellite cells, immune cells and endothelial cells in SkM according to CR or EX. NicheNet analysis, exploring potential inter-organ communication, indicates that BAT and SkM can mutually regulate their fatty acid metabolism and thermogenesis by ligands and receptors. These data comprise an extensive resource for thermogenic tissues molecular responses to CR and/or EX in healthy state. Calorie restriction (CR) and exercise training (EX) are two critical lifestyles for the prevention and treatment of metabolic diseases, such as obesity and diabetes. Brown adipose tissue (BAT) and skeletal muscle (SkM) are two important organs to generate heat. Here we provide detailed transcriptional profiling of these two thermogenic tissues from mice treated with CR and/or EX. We demonstrate the transcriptional reprogramming of BAT and SkM according to CR, but little to EX. Consistent with this, CR induces genes encoding adipokines or myokines alteration in BAT and SkM, respectively. Deconvolution analysis implies differences of subpopulations of myogenic cells, mesothelial cells and endogenic cells in BAT, and demonstrates differences of subpopulations of satellite cells, immune cells and endothelial cells in SkM according to CR or EX. NicheNet analysis, exploring potential inter-organ communication, indicates that BAT and SkM can mutually regulate their fatty acid metabolism and thermogenesis by ligands and receptors. These data comprise an extensive resource for thermogenic tissues molecular responses to CR and/or EX in healthy state.
2023-12-12 | GSE222163 | GEO
Project description:Chromium (Cr) is a non-essential metal for normal plants and is toxic to plants at high concentration. In spite of many previous studies having been conducted on the effects of Cr stress, the precise molecular mechanisms and signaling pathways of action of Cr remain poorly understood. In this study, the transcriptome at the early of Cr (VI) stress were assayed in rice roots. To gain more insight into these cellular responses, we analyzed whole-genome transcriptome of rice expose to Cr (VI) for 1 and 3 h. Analysis revealed 1,261 and 267 up and down-regulated genes by Cr (VI). Cr (VI) stress triggered changes in transcript levels of genes related to secondary metabolism process, biosynthetic process, specially jasmonic acid biosynthetic process, response to abiotic stress, specially response to toxin, transcription regulator activity, specially transcription factors activity. The most predominant transcription factor families were WRKY, AP2/ERF, NAC, C2H2, MYB. In addition, many protein kinase, including eight MAPKKK, two CDPK, and one MAPK, showed significant increase in transcriptional level under Cr (VI) stress. Molecular mechanisms for the excess Cr(VI) in rice roots Comparison of mock control and rice seedlings treated with 200 M-NM-<M Cr(VI); Biological replicates: 3 control replicates, 3 Cr(VI)-treated replicates.
2013-10-31 | E-GEOD-33376 | biostudies-arrayexpress
Project description:Obesity is characterized by excess energy storage which results in dysfunctional white adipose tissue (WAT) and in turn leads to metabolic diseases. Lifestyle changes especially calorie restriction (CR) reduces the risk for age and obesity-associated complications. The impact of CR on obesity has mainly been examined with human intervention studies, which indicated alterations in circulating adipokines. However, a detailed understanding of CR-induced adipocyte secretome changes remains elusive. Therefore, we investigated the effect of CR on the secretion profile of mature human adipocytes by using proteomics technology with bioinformatic analysis. We demonstrated CR-mediated adipocyte triglyceride reduction, which resulted in a positive effect on adipokine secretion indicating an improved inflammatory phenotype and alleviation of obesity-associated metabolic dysfunction including insulin resistance and glucose intolerance. Furthermore, 6 novel adipocyte-secreted proteins were identified which were regulated by CR. Since resveratrol (RSV) mimics CR we compared results from this study with data from our previous RSV study on the adipocyte secretome. We observed that both treatment strategies lead to a less inflammatory phenotype and an altered adipokine profile indicating improvement of metabolic complications even though the CR and RSV adipocyte secretomes differed from each other.
2016-05-25 | PXD000301 | Pride