Comparative proteome analysis of brown adipose tissue in obese C57BL/6J mice using iTRAQ-coupled 2D LC-MS/MS

• Published in: PloS one 2015-03, Vol.10 (3), p.e0119350-e0119350
• Main Authors: Li, Juan, Zhao, Wei-Gang, Shen, Zhu-Fang, Yuan, Tao, Liu, Shuai-Nan, Liu, Quan, Fu, Yong, Sun, Wei
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes, Brown - metabolism; Adipocytes, Brown - pathology; Adipose tissue; Adipose tissue (brown); Adipose Tissue, Brown - metabolism; Adipose Tissue, Brown - pathology; Animals; Apoptosis; Apoptosis-inducing factor; Body fat; Body weight; Brown adipose tissue; Cardiovascular diseases; Care and treatment; Carnitine; Carnitine O-palmitoyltransferase; Cytochrome; Development and progression; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diet; Endocrinology; Energy expenditure; Energy metabolism; Enzymes; Fatty acids; Female; Functional analysis; Gangrene; Gene Expression Regulation; Health aspects; Health risks; High fat diet; Hospitals; Insulin; Laboratory animals; Mass Spectrometry; Metabolism; Mice; Mitochondria; Obesity; Obesity - metabolism; Obesity - pathology; Overweight; Oxidation; Palmitoyltransferase; Proteins; Proteome - biosynthesis; Proteomes; Proteomics - methods; Rodents; Science; Scientific imaging; Sensitivity analysis; Uncoupling protein 1; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0119350

High-fat diet (HFD) leads to the development of obesity accompanied by insulin resistance, which increases the risk of type 2 diabetes mellitus and cardiovascular disease. Brown adipose tissue (BAT) plays an essential role in energy metabolism, thus it will give us promising treatment targets through elucidating underlying mechanisms of BAT in obesity. In this study, female C57BL/6J mice were fed HFD or normal diet (ND) for 22 weeks. Hyperinsulinemic-euglycemic clamp was performed to evaluate insulin sensitivity, which was independently correlated with obesity. Using isobaric tag for relative and absolute quantification (iTRAQ) coupled with 2D LC-MS/MS, we quantitated 3048 proteins in BAT. As compared HFD with ND, we obtained 727 differentially expressed proteins. Functional analysis found that those proteins were mainly assigned to the pathway of mitochondrial function. In this pathway, carnitine O-palmitoyltransferase 2 (CPT2), uncoupling protein 1 (UCP1) and apoptosis-inducing factor 1 (AIF1) were up-regulated significantly by HFD, and they were confirmed by western blotting. The results indicated that HFD might induce the apoptosis of brown adipocytes via the up-regulated AIF1. Meanwhile, HFD also stimulated fatty acid β-oxidation and raised compensatory energy consuming through the increases of CPT2 and UCP1, respectively. However, the apoptosis of brown adipocytes might weaken the compensatory energy expenditure, and finally contribute to overweight/obesity. So, preventing the apoptosis of brown adipocytes may be the key target to treat obesity.