Comparative proteome analysis of brown adipose tissue in obese C57BL/6J mice using iTRAQ-coupled 2D LC-MS/MS.
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.
Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Juan
J
Li
Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Wei-Gang
WG
Zhao
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China.
Zhu-Fang
ZF
Shen
Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Tao
T
Yuan
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China.
Shuai-Nan
SN
Liu
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, China.
Quan
Q
Liu
Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Yong
Y
Fu
Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences/School of Basic Medicine, Peking Union Medical College, Beijing, China.
Wei
W
Sun
D052437:Adipocytes, Brown / Q000378:metabolism* / Q000473:pathology; D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D013058:Mass Spectrometry; D051379:Mice; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D020543:Proteome / Q000096:biosynthesis*; D040901:Proteomics / Q000379:methods
D020543:Proteome