Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dietary intervention improves health metrics and life expectancy of the genetically obese Titan mouse

ABSTRACT: Suitable animal models are essential for translational research, especially in the case of complex, multifactorial conditions, such as obesity. The non-inbred mouse (Mus musculus) line Titan, also known as DU6, is one of the world’s longest selection experiments for high body mass and was previously described as a model for metabolic healthy (benign) obesity. The present study further characterizes the geno- and phenotypes of this non-inbred mouse line and testes its suitability as an interventional obesity model. In contrast to previous findings, our data suggest that Titan mice are metabolically unhealthy obese and short-lived. Line-specific patterns of genetic invariability are in accordance with observed phenotypic traits. Titan mice also show modifications in the liver transcriptome, proteome, and epigenome linked to metabolic (dys)regulations. Importantly, dietary intervention partially reversed the metabolic phenotype in Titan mice and significantly extended their life expectancy. Therefore, the Titan mouse line is a valuable resource for translational and interventional obesity research

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Christina Ludwig

LAB HEAD: Christina Ludwig

PROVIDER: PXD019030 | Pride | 2022-05-04

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	BBM_181_P095_02_FRH_01.raw	Raw
	BBM_181_P095_02_FRH_02.raw	Raw
	BBM_181_P095_02_FRH_03.raw	Raw
	BBM_181_P095_02_FRH_04.raw	Raw
	BBM_181_P095_02_FRH_05.raw	Raw

Items per page:

1 - 5 of 53

Similar Datasets

Differential proteomics of the synaptosomal fraction from rat dentate gyrus identified the changes associated with aging-dependent cognitive decline

Project description:The study contained three groups of Sprague-Dawley male rats – two groups of aging animals (22-24 months) separated based on performance in spatial reference memory task; and the third, control group of young animals () not separated by behavioural testing. The synaptosome – enriched membrane fraction of the dentate gyrus was isolated from nine randomly chosen individuals per group and analysed by tandem mass tag (TMT) labelling and mass spectrometry (MS)-based quantitative proteomics. The proteomic experiment was performed in three TMT10plex sets, with each set containing samples from three biological replicates per group and one TMT 126 reference channel reserved to directly compare the protein intensities across the entire study. The peptides were analysed in two parallel MS runs representing two technical replicates per biological sample. The total number of 6513 protein entries was identified of which 471 showed a significantly changed level (p<0.05) in any of the three animal groups. The comparison between aged and young animals revealed 293 significantly changed proteins (p<0.05) in aged good performers vs young rats, and 310 significant proteins (p < 0.05) in aged bad performers vs young ones. The proteomic differences between aged good vs bad performers were represented by 78 significantly changed proteins (p < 0.05).

2019-08-19 | PXD013172 | Pride

Alterations in lipid profile of the aging kidney identified by MALDI imaging mass spectrometry

Project description:During aging, the kidney undergoes functional and physiological changes that are closely affiliated with chronic kidney disease (CKD). There is increasing evidence supporting the role of lipid or lipid-derived mediators in the pathogenesis of CKD and other aging-related diseases. To understand the role of lipids in various metabolic processes during kidney aging, we conducted MALDI imaging mass spectrometry (MALDI-IMS) analysis in kidneys harvested from young (2 months old, n=3) and old mice (24 months old, n=3). MALDI-IMS analysis showed an increase in ceramide level and a decrease in sphingomyelin (SM) and phosphatidylcholine (PC) levels in kidneys of old mice. The increased expression of cPLA2 and SMPD1 protein in aged kidney was confirmed by immunohistochemistry and western blot analysis. Our MALDI-IMS data showed the altered distribution of lipids in aged kidney as indicative of aging-related functional changes of the kidney. Combined analysis of MALDI-IMS and IHC confirmed lipidomic changes and expression levels of responsible enzymes as well as morphological changes.

2019-06-10 | PXD013860 | Pride

RNAseq of whole ovarian follicles from young and old mice.

Project description:Compare gene expression in whole ovarian follicles from young (6-12 weeks) and old (14-17 months) mice. Whole follicles,consist of the oocyte and granulosa cells. As oocytes are very difficult to extract intact from old follicles due to fibrosis, whole follicles were sequenced instead, so that old and young could be properly compared. 2-3 follicles each were sequenced from 4 old mice and 5 young mice. Each sample has both single- and paired-end runs.

2018-05-22 | E-MTAB-5952 | biostudies-arrayexpress

Plants encode a general siRNA suppressor that is induced and suppressed by viruses

Project description:Small RNAs play essential regulatory roles in genome stability, development and stress responses in most eukaryotes. Plants encode DICER-LIKE (DCL) RNaseIII enzymes, including DCL1, which produces miRNAs, and DCL2, DCL3 and DCL4, which produce diverse size classes of siRNA. Plants also encode RNASE THREE-LIKE (RTL) enzymes that lack DCL-specific domains and whose function is largely unknown. Small RNA sequencing in plants over-expressing RTL1 or RTL2 or lacking RTL2 revealed that RTL1 over-expression inhibits the accumulation of all types of small RNAs produced by DCL2, DCL3 and DCL4, indicating that RTL1 is a general suppressor of plant siRNA pathways. By contrast, RTL2 plays minor, if any, role in the small RNA repertoire. In vivo and in vitro assays revealed that RTL1 prevents siRNA production by degrading dsRNA before they are processed by DCL2, DCL3 and DCL4. The substrate of RTL1 cleavage is likely long perfect (or near-perfect) dsRNA, consistent with the RTL1-insensitivity of miRNAs, which derive from short imperfect dsRNA. RTL1 is naturally expressed only weakly in roots, but virus infection strongly induces its expression in leaves, suggesting that RTL1 induction is a general strategy used by viruses to counteract the siRNA-based plant antiviral defense. Accordingly, transgenic plants over-expressing RTL1 are more sensitive to TYMV infection than wild-type plants, likely because RTL1 prevents the production of antiviral siRNAs. However, TCV, TVCV and CMV, which encode stronger suppressors of RNA silencing (VSR) than TYMV, are insensitive to RTL1 over-expression. Indeed, TCV VSR inhibits RTL1 activity, suggesting that inducing RTL1 expression and dampening RTL1 activity is a dual strategy used by viruses to establish a successful infection. These results reveal another level of complexity in the evolutionary battle between viruses and plant defenses. Flower sRNA profiles in diverse conditions involving RTL1 and RTL2

2013-09-10 | E-GEOD-49866 | biostudies-arrayexpress

Age-associated changes in human CD4+ T cells point to mitochondrial dysfunction consequent to impaired autophagy

Project description:To gain understanding on the mechanisms that drive immunosenescence in humans, we examined CD4+ T cells obtained from younger (20-39 years-old) and older (70+ years-old) healthy participants of the Baltimore Longitudinal Study on Aging (BLSA). We found that mitochondrial proteins involved in the electron transport chain were overrepresented in cells from older participants, with prevalent dysregulation of oxidative phosphorylation and energy metabolism molecular pathways. Surprisingly, gene transcripts coding for mitochondrial proteins pertaining to oxidative phosphorylation and electron transport chain pathways were underrepresented in older individuals. Paralleling the observed decrease in gene expression, mitochondrial respiration was impaired in CD4+ T cells from older subjects. Though mitochondrial number in both naïve and memory cells visualized with electron microcopy was similar in older versus younger participants, there were a significantly higher number of autophagosomes, many of them containing undegraded mitochondria, in older individuals. The presence of mitochondria inside the accumulated autophagic compartments in CD4+ T cells from older individuals was confirmed by immunofluorescence. These findings suggest that older age is associated with persistence of dysfunctional mitochondria in CD4+ T lymphocytes caused by defective mitochondrial turnover by autophagy, which may trigger chronic inflammation and contribute to the impairment of immune defense in older persons.

2019-11-27 | PXD016039 | Pride

Organ-specific inflammaging in mice

Project description:Aging is accompanied by chronic, low-grade systemic inflammation, termed inflammaging, a main driver of age-associated diseases. Such sterile inflammation is typically characterized by elevated levels of pro-inflammatory mediators, such as cytokines and reactive oxygen species causing organ damage. Lipid mediators play important roles in the fine-tuning of both the promotion and the resolution of inflammation. Yet, it remains unclear how lipid mediators fit within the concept of inflammaging and how their biosynthesis and function is affected by aging. Here, we provide comprehensive signature profiles of inflammatory markers in organs afflicted with inflammation of young and old C57BL/6 mice. We reveal an organ-specific footprint of inflammation-related cytokines, chemokines and lipid mediators, which are distinctively affected by aging. While some organs are characterized by a pronounced pro-inflammatory microenvironment and impaired resolution during aging, others display elevated levels of pro-resolving mediators or an overall decrease in inflammatory signaling. Our results demonstrate that it proves difficult to establish a unifying concept for alterations of immunomodulatory mediators as consequence of aging and that organ specificity needs to be considered. Moreover, our data imply that inclusion of lipid mediators into the concept of inflammaging provides a comprehensive tool to characterize the inflammatory microenvironment during aging on a broader and yet, more detailed scope.

2021-03-22 | PXD024356 | Pride

Microarray Analysis of Gene Expression in Human Normal and Breast Cancer Cells

Project description:Differential gene expression between normal breast epithelial cells and the malignant counterpart was studied using microarray technique. We utilized GeneAlbum GEM 1-6 from Incyte Pharmaceuticals, Inc., which contains which contains 65,873 cDNA clones (57,172 clones excluding controls), representing 33,515 individual genes. The normal human mammary epithelial cells (HMEC) from 3 donors were used to search different gene expression patterns among individuals, ages and races. In addition, 8 well-established breast cancer cell lines were used as probes against a common normal HMEC from 50 years old donor

2010-06-10 | E-GEOD-2155 | biostudies-arrayexpress

Obesity-mediated regulation of the cardiac acetylome

Project description:Lysine residues undergo diverse and reversible post-translational modifications including acetylation. Acetylation of lysine residues have traditionally been studied as epigenetic modifiers of histone tails within chromatin that provides an important mechanism for regulating gene expression. In the heart, histone acetylation acts as a key regulator of cardiac remodeling and function. However, recent studies have shown that thousands of proteins (~4,500) can be acetylated at multiple acetylation sites (~15,000 sites). These data suggest that the acetylome rivals phosphorylation in prevalence as a post-translational modification. Based on this, we examined the impact of obesity on the regulation of lysine acetylation in the left ventricle of male c57BL/6J mice. We report that obesity contributed to a significant increase in heart enlargement and fibrosis. Of interest, immunoblot analysis demonstrated that lysine acetylation was markedly altered in response to diet-induced obesity and that this phenomena was cardiac tissue specific. Mass spectral analysis was performed in which 3264 proteins were identified in the left ventricle. Of these, 254 proteins were acetylated, 16 of which were significantly impacted by obesity. Ingenuity Pathway Analysis identified the Cardiovascular Disease network as significantly regulated by obesity, 54 of the 254 acetylated proteins impact this pathway. This network includes LIM domain-binding protein 3 (LDB3), aconitate hydratase (ACO2), and dihydrolipoyl dehydrogenase (DLD), which are all significantly impacted by obesity and known to regulate cardiac function. Combined, these findings suggest a critical role for the cardiac acetylome in obesity-mediated remodeling and ultimately have the potential to elucidate novel targets that regulate cardiac pathology.

2018-08-06 | PXD008385 | Pride

CRISPR-Cas9 genetic screen leads to the discovery of L-Moses, a KAT2B inhibitor that attenuates Tunicamycin-mediated neurodegeneration

Project description:Accumulation of aggregated and misfolded proteins, leading to endoplasmic reticulum stress and activation of the unfolded protein response, is a hallmark of several neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease. Genetic screens are powerful tools that are proving invaluable in identifying novel modulators of disease associated processes. Here, we performed a loss-of-function genetic screen using a human druggable genome library, followed by an arrayed-screen validation, in human iPSC-derived cortical neurons. We identified 13 genes, whose knockout was neuroprotective against Tunicamycin, a glycoprotein synthesis inhibitor widely used to induce endoplasmic reticulum stress. We also demonstrated that pharmacological inhibition of KAT2B, a lysine acetyltransferase identified by our genetic screens, by L-Moses, attenuates Tunicamycin-mediated neuronal cell death and activation of CHOP, a key pro-apoptotic member of the unfolded protein response in both cortical and dopaminergic neurons. Follow-up transcriptional analysis suggested that L-Moses provided neuroprotection by partly reversing the transcriptional changes caused by Tunicamycin. Finally, L-Moses treatment attenuated the total protein levels affected by Tunicamycin, without affecting their acetylation profile. In summary, using an unbiased approach, we identified KAT2B and its inhibitor, L-Moses, as potential therapeutic targets for neurodegenerative diseases.

2023-03-10 | PXD038395 | Pride

Gene expression profiling of human mammary artery media during aging

Project description:Our goal was to better understand the genes and pathways implicated during arterial media aging. We therefore compared the gene expression profile of human mammary artery media between Young (<60, 8 patients) and old (>75, 7 patients) patients. The microarray data, generated using the Illumina sentrix Ref8-V2 platform, was normalized and analyzed using the IlluminaGUI package (Eggle and Schultze, 2007). We used 8 samples from the "Young" groups and 7 samples from the "old" group. No technical replicates were used.

2010-12-07 | E-GEOD-16487 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data