title: Protein sets define disease states and predict in vivo effects of drug treatment.
abstract: Gaining understanding of common complex diseases and their treatments are the main drivers for life sciences. As we show here, comprehensive protein set analyses offer new opportunities to decipher functional molecular networks of diseases and assess the efficacy and side-effects of treatments in vivo. Using mass spectrometry, we quantitatively detected several thousands of proteins and observed significant changes in protein pathways that were (dys-) regulated in diet-induced obesity mice. Analysis of the expression and post-translational modifications of proteins in various peripheral metabolic target tissues including adipose, heart, and liver tissue generated functional insights in the regulation of cell and tissue homeostasis during high-fat diet feeding and medication with two antidiabetic compounds. Protein set analyses singled out pathways for functional characterization, and indicated, for example, early-on potential cardiovascular complication of the diabetes drug rosiglitazone. In vivo protein set detection can provide new avenues for monitoring complex disease processes, and for evaluating preclinical drug candidates.
authors.affiliation: Otto Warburg Laboratory, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Meierhofer
authors.forename: Christopher
authors.initials: C
authors.lastname: Weidner
authors.forename: Ludger
authors.initials: L
authors.lastname: Hartmann
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Mayr
authors.forename: Chung-Ting
authors.initials: CT
authors.lastname: Han
authors.forename: Frank C
authors.initials: FC
authors.lastname: Schroeder
authors.forename: Sascha
authors.initials: S
authors.lastname: Sauer
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D000077154:Rosiglitazone; D012459:Salicylates / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012459:Salicylates; D045162:Thiazolidinediones; D000077154:Rosiglitazone