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

Li J, Zhao WG, Shen ZF, Yuan T, Liu SN, Liu Q, Fu Y, Sun W - PLoS ONE (2015)

Bottom Line: 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.The results indicated that HFD might induce the apoptosis of brown adipocytes via the up-regulated AIF1.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

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Differential proteins between HFD and ND group in BAT were analyzed through the PANTHER classification system.(A) Cell Component of whole genome, BAT protein profile and the differentially expressed proteins in BAT. (B) Molecular Function assigned to whole genome, BAT protein profile and the differentially expressed proteins in BAT. (C) Biological processes assigned to whole genome, BAT protein profile and the differentially expressed proteins in BAT.
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pone.0119350.g003: Differential proteins between HFD and ND group in BAT were analyzed through the PANTHER classification system.(A) Cell Component of whole genome, BAT protein profile and the differentially expressed proteins in BAT. (B) Molecular Function assigned to whole genome, BAT protein profile and the differentially expressed proteins in BAT. (C) Biological processes assigned to whole genome, BAT protein profile and the differentially expressed proteins in BAT.

Mentions: These differential proteins were preliminary analyzed according to GO database (http://www.pantherdb.org/). 34.3% of differential proteins were assigned to cell part. We also observed that HFD increased the expression of membrane proteins (Fig. 3A). The molecular function and biological process of the differentially expressed proteins were also annotated. 38.1% of differential proteins were assigned to catalytic activity in BAT and 11.5% of differential proteins involved in structural molecule activity were regulated (Fig. 3B). It indicated that BAT was rich in proteins which involved in catalytic activity and structural molecule activity, as compared BAT profile with whole genome. HFD increased the amount of proteins which were assigned to transporter activity. Moreover, the proportion of differentially expressed proteins (35.5%) involved in metabolic process was higher than which of total BAT proteins (33.1%) and whole genome profile (27.0%) (Fig. 3C). It suggested that HFD stimulated the activity of proteins that related to metabolism.


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

Li J, Zhao WG, Shen ZF, Yuan T, Liu SN, Liu Q, Fu Y, Sun W - PLoS ONE (2015)

Differential proteins between HFD and ND group in BAT were analyzed through the PANTHER classification system.(A) Cell Component of whole genome, BAT protein profile and the differentially expressed proteins in BAT. (B) Molecular Function assigned to whole genome, BAT protein profile and the differentially expressed proteins in BAT. (C) Biological processes assigned to whole genome, BAT protein profile and the differentially expressed proteins in BAT.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352050&req=5

pone.0119350.g003: Differential proteins between HFD and ND group in BAT were analyzed through the PANTHER classification system.(A) Cell Component of whole genome, BAT protein profile and the differentially expressed proteins in BAT. (B) Molecular Function assigned to whole genome, BAT protein profile and the differentially expressed proteins in BAT. (C) Biological processes assigned to whole genome, BAT protein profile and the differentially expressed proteins in BAT.
Mentions: These differential proteins were preliminary analyzed according to GO database (http://www.pantherdb.org/). 34.3% of differential proteins were assigned to cell part. We also observed that HFD increased the expression of membrane proteins (Fig. 3A). The molecular function and biological process of the differentially expressed proteins were also annotated. 38.1% of differential proteins were assigned to catalytic activity in BAT and 11.5% of differential proteins involved in structural molecule activity were regulated (Fig. 3B). It indicated that BAT was rich in proteins which involved in catalytic activity and structural molecule activity, as compared BAT profile with whole genome. HFD increased the amount of proteins which were assigned to transporter activity. Moreover, the proportion of differentially expressed proteins (35.5%) involved in metabolic process was higher than which of total BAT proteins (33.1%) and whole genome profile (27.0%) (Fig. 3C). It suggested that HFD stimulated the activity of proteins that related to metabolism.

Bottom Line: 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.The results indicated that HFD might induce the apoptosis of brown adipocytes via the up-regulated AIF1.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus