Phosphoprotein network analysis of white adipose tissues unveils deregulated pathways in response to high-fat diet

• DOI: 10.1038/srep25844
• Publication Date: 2016-05-16T09:35:11Z
• Authors: Asfa Alli Shaik; Beiying Qiu; Sheena Wee; Hyungwon Choi; Jayantha Gunaratne; Vinay Tergaonkar
• Keywords: Phosphoprotein; White (mutation)

Abstract Despite efforts in the last decade, signaling aberrations associated with obesity remain poorly understood. To dissect molecular mechanisms that define this complex metabolic disorder, we carried out global phosphoproteomic analysis of white adipose tissue (WAT) from mice fed on low-fat diet (LFD) and high-fat (HFD). We quantified phosphorylation levels 7696 peptides, found significant differential 282 phosphosites 191 proteins, including various insulin-responsive proteins enzymes involved lipid homeostasis response to feeding. Kinase-substrate prediction integrated network altered phosphoproteins revealed underlying modulations during HFD-induced obesity, suggested deregulation lipogenic lipolytic pathways. Mutation differentially-regulated novel phosphosite cytoplasmic acetyl-coA forming enzyme ACSS2 (S263A) upon led accumulation serum triglycerides reduced AKT as compared wild type ACSS2, thus highlighting its role obesity. Altogether, our study presents a comprehensive map phosphoproteome reveals many previously unknown candidate sites for future functional investigation.