Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profile from short-term caloric restriction in mouse adipose tissue

ABSTRACT: 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-Î²) 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).

ORGANISM(S): Mus musculus

SUBMITTER: Cheol-Koo Lee

PROVIDER: E-GEOD-60596 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Whole-transcriptome analysis of mouse adipose tissue in response to short-term caloric restriction.

Kim Seung-Soo SS Choi Kyung-Mi KM Kim Soyoung S Park Taesun T Cho In-Cheol IC Lee Jae-Won JW Lee Cheol-Koo CK

Molecular genetics and genomics : MGG 20151125 2

Caloric restriction (CR) has been shown to extend the lifespan of many species by improving cellular function and organismal health. Additionally, fat reduction by CR may play an important role in lengthening lifespan and preventing severe age-related diseases. Interestingly, CR induced the greatest transcriptome change in the epididymal fat of mice in our study. In this transcriptome analysis, we identified and categorized 446 genes that correlated with CR level. We observed down-regulation of ...[more]

PMID: 26606930

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Project description:Background: Calorie restriction (CR) is the only intervention known to extend lifespan in a wide range of organisms, including mammals. However, the mechanisms by which it regulates mammalian aging remain largely unknown and the involvement of the TOR and Sirtuin pathways (which regulate aging in lower organisms) remain controversial. Femaleness is a second phenotype generally associated with longevity but the relationship between sex-biased and CR-induced gene expression remains undetermined. Methodology/Principal Findings: We generated microarray gene expression data from livers of male mice fed high calorie or CR diets, and we find that CR significantly changes the expression of over 3,000 genes, many between 10- and 50-fold. We compare our data to the GenAge database of known aging-related genes and to prior microarray expression data of genes expressed differently between male and female mice. CR generally feminizes gene expression and many of the most significantly changed individual genes are involved in aging, hormone signaling, and p53-associated regulation of the cell cycle and apoptosis. Among the genes showing the largest and most statistically significant CR-induced expression differences are Ddit4, a key regulator of the TOR pathway, and Nnmt, a regulator of lifespan linked to the Sirtuin pathway. Using Western analyses, we confirmed post-translational inhibition of the TOR pathway. Conclusions: Our data show that CR induces widespread gene expression changes and acts through highly evolutionarily conserved pathways, from microorganisms to mammals, and that its life-extension effects might arise partly from a shift toward a gene expression profile more typical of the longer-lived female sex. Keywords: Two-class gene expression comparison. Calorie restriction (CR) versus HIGH CALORIE feeding. Design of the experiment is a two-class paired design in which the two classes are HIGH CALORIE and CALORIE RESTRICTION (CR) dietary regimens fed to mice, resulting in 15 HIGH CALORIE microarrays and 8 CR microarrays; 23 total microarrays. Four HIGH CALORIE and 2 CR microarrays were produced using pools of 3 RNA samples for each microarray (6 pools of 3, plus 17 individual samples = 35 individual mouse liver samples, 23 microarrays). Total liver RNA was labeled directly. Reference RNA: Stratagene Universal Mouse Reference RNA.

Project description:With the internationalization of traditional Chinese medicine, the demand for medicinal and edible Codonopsis Radix (CR) is increasing, and its medicinal resources have attracted atten- tion. CR is a famous traditional Chinese medicine with a long pharmaceutical and edible history. Guizhou has abundant CR resources, but in the absence of systematic studies on species identifi- cation and chemical compositions, it has not been fully utilized. The results of plant traits and DNA barcoding molecular identification indicated that Luodang (LD) and Weidang (WD) from Guizhou were Codonopsis tangshen, C. pilosula., respectively. Widely targeted metabolomics analysis revealed that a total of 1116 metabolites from 14 categories, including phenolic acids, lipids, flavonoids, etc., were found in LD, WD, and the three Chinese Pharmacopoeia CR. CRs shared 1054 (94.4%) me- tabolites, with extremely similar metabolite profiles. Affected by Guizhou's particular climate, LD and WD each contained 3 and 10 dominant differential metabolites, respectively, which were pri- marily flavonoids and amino acids. Amino acids, phenolic acids, and organic acids play important roles in the excellent food attributes of them. In CR, 8 dominant differential metabolites were dis- covered for the first time, including isoorientin-7-O-(6′′-feruloyl) glucoside, N-formyl-L-methionine, and cyclo (Phe-Glu), etc. Network pharmacology analyses showed that LD dominant differential metabolites were closely related to anti-tumor, cardiovascular disease improvement, nervous system protection, and metabolic disease treatment, whereas WD was closely related to nervous system protection and cardiovascular disease improvement. In conclu- sion, LD and WD can be used and promoted medicinally as CR and have potential value for new drug development. This work enriched the database of CR compounds and provided a reference for quality control, resource development, and new drug development of CR

Dataset Information

Gene expression profile from short-term caloric restriction in mouse adipose tissue

Publications

Whole-transcriptome analysis of mouse adipose tissue in response to short-term caloric restriction.

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