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.
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.
authors.affiliation: Max Planck Institute for Molecular Genetics , Ihnestraße 63-73, 14195 Berlin, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Meierhofer
authors.forename: Christopher
authors.initials: C
authors.lastname: Weidner
authors.forename: Sascha
authors.initials: S
authors.lastname: Sauer
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D020869:Gene Expression Profiling; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D040901:Proteomics; D000077154:Rosiglitazone; D053719:Tandem Mass Spectrometry; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D059467:Transcriptome
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone
keywords: biomarkers; mass spectrometry; molecular pathways; network analysis; obesity; type 2 diabetes