Bridging the Gap Between Protein-tyrosine Phosphorylation Networks, Metabolism and Physiology in Liver-specific PTP1b Deletion Mice
Author | : Emily Rae Miraldi |
Publisher | : |
Total Pages | : 182 |
Release | : 2012 |
ISBN-10 | : OCLC:806957068 |
ISBN-13 | : |
Rating | : 4/5 ( Downloads) |
Download or read book Bridging the Gap Between Protein-tyrosine Phosphorylation Networks, Metabolism and Physiology in Liver-specific PTP1b Deletion Mice written by Emily Rae Miraldi and published by . This book was released on 2012 with total page 182 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metabolic syndrome describes a complex set of obesity-related disorders that enhance diabetes, cardiovascular, and mortality risk. Studies of liver-specific protein-tyrosine phosphatase lb (PTPlb) deletion mice (L-PTPlb-/-) suggests that hepatic PTPlb inhibition would mitigate metabolic syndrome progression through amelioration of hepatic insulin resistance, endoplasmic reticulum stress, and whole-body lipid metabolism. However, the network alterations underlying these phenotypes are poorly understood. Mass spectrometry was used to quantitatively discover protein phosphotyrosine network changes in L-PTP lb-/- mice relative to control mice under both normal and high-fat diet conditions. A phosphosite set enrichment analysis was developed to identify numerous pathways exhibiting PTPlb- and diet-dependent phosphotyrosine regulation. Detection of PTP lb-dependent phosphotyrosine sites on lipid metabolic proteins initiated global lipidomics characterization of corresponding liver samples and revealed altered fatty acid and triglyceride metabolism in L-PTPlb-/- mice. Multivariate modeling techniques were developed to infer molecular dependencies between phosphosites and lipid metabolic changes, resulting in quantitatively predictive phenotypic models.