Western Diet Alters Phosphorylation and O‐GlcNAcylation of Proteins Involved in Mouse Heart Metabolic Disease

Abstract

The Western style diet (high fat and high sucrose) has lead to an epidemic of unfavorable metabolic disorders associated with obesity, diabetes and hyperlipidemia; leading to cardiovascular disease (CVD). Our hypothesis is that poor diet causes unfavorable metabolic conditions due to changes in post‐translational modifications (PTMs) of proteins in heart tissue. Two key PTMs that are perturbed in metabolically diseased tissues are phosphorylation and O‐GlcNAcylation. Both phosphorylation and O‐GlcNAcylation are found on nucleocytoplasmic proteins, regulate one another at the same serine/threonine site or adjacent sites, and are induced by insulin, nutrients (glucose), stress and other factors. 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). Label‐free quantification was conducted using Scaffold and Progenesis. Using IPA software revealed a number of cardiovascular disease related proteins with altered levels. Upon further manual inspection many of the key proteins in normal heart function had altered phosphorylation and O‐GlcNAcylation modifications due to the Western diet. Some of these altered PTMs correlated with metabolic disease related mechanisms. NIH‐NHLBI Contract No. HHSN268201000031C and NIH‐GM grant P41 GM104603.