Metabolic Disorder in a Mouse Model on an American Diet: Proteomic Analysis of Cardiovascular Disease

Abstract

Unfavorable metabolic conditions (metabolic disorders) associated with obesity, diabetes, and hyperlipidemia are major causes for cardiovascular disease (CVD). One major environmental cause of this may be attributed to poor diet, aka the American diet. The early detection and monitoring of the adverse effects of metabolic disease on the heart and vasculature, although well studied, remain elusive. Our hypothesis is that poor diet causes unfavorable metabolic conditions in heart tissue resulting in inflammation and oxidative stress reflected in protein changes. Here we apply label‐free proteomics to elucidate potential biomarkers of CVD including both protein changes and changes in post‐translational modifications (PTMs). Heart tissue was from control mice and mice fed a high fat high sucrose diet (HFHS). MS/MS data was analyzed with Proteome Discoverer and Mascot software, using both variable‐modification and error‐tolerant search modes. Label‐free quantification was conducted using Scaffold and Progenesis; typically yielding >;1,000 features. Using IPA software revealed a number of cardiovascular disease related proteins were observed. This is the first step in biomarker panel development for disease diagnosis and progression. This project was funded by NIH‐NCRR grants P41 RR010888/GM104603, S10 RR015942, S10 RR020946, S10 RR025082 and NIH‐NHLBI contract N01 HV00239.