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Integrative analysis of transcriptomics, proteomics, and metabolomics data of white adipose and liver tissue of high-fat diet and rosiglitazone-treated insulin-resistant mice identified pathway alterations and molecular hubs

Item Type:Article
Title:Integrative analysis of transcriptomics, proteomics, and metabolomics data of white adipose and liver tissue of high-fat diet and rosiglitazone-treated insulin-resistant mice identified pathway alterations and molecular hubs
Creators Name:Meierhofer, D. and Weidner, C. and Sauer, S.
Abstract:The incidences of obesity and type 2 diabetes are rapidly increasing and have evolved into a global epidemic. In this study, we analyzed the molecular effects of high-fat diet (HFD)-induced insulin-resistance on mice in two metabolic target tissues, the white adipose tissue (WAT) and the liver. Additionally, we analyzed the effects of drug treatment using the specific PPARγ ligand rosiglitazone. We integrated transcriptome, proteome, and metabolome data sets for a combined holistic view of molecular mechanisms in type 2 diabetes. Using network and pathway analyses, we identified hub proteins such as SDHB and SUCLG1 in WAT and deregulation of major metabolic pathways in the insulin-resistant state, including the TCA cycle, oxidative phosphorylation, and branched chain amino acid metabolism. Rosiglitazone treatment resulted mainly in modulation via PPAR signaling and oxidative phosphorylation in WAT only. Interestingly, in HFD liver, we could observe a decrease of proteins involved in vitamin B metabolism such as PDXDC1 and DHFR and the according metabolites. Furthermore, we could identify sphingosine (Sph) and sphingosine 1-phosphate (SP1) as a drug-specific marker pair in the liver. In summary, our data indicate physiological plasticity gained by interconnected molecular pathways to counteract metabolic dysregulation due to high calorie intake and drug treatment.
Keywords:Type 2 Diabetes, Obesity, Mass Spectrometry, Molecular Pathways, Biomarkers, Network Analysis, Animals, Mice
Source:Journal of Proteome Research
ISSN:1535-3893
Publisher:American Chemical Society (U.S.A.)
Volume:13
Number:12
Page Range:5592-5602
Date:5 December 2014
Additional Information:Erratum in: J Proteome Res 14(3):1643.
Official Publication:https://doi.org/10.1021/pr5005828
PubMed:View item in PubMed

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