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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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Related in: MedlinePlus

Body weight and metabolic status of mice were affected by HFD.HFD significantly altered the body weight (A), and induced glucose intolerance (B) in C57BL/6J mice. Black circle = Normal diet group, black squares = High-fat diet group. Data are mean ± SEM (n = 6), *p<0.05, **p<0.01, ***p<0.001.
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pone.0119350.g002: Body weight and metabolic status of mice were affected by HFD.HFD significantly altered the body weight (A), and induced glucose intolerance (B) in C57BL/6J mice. Black circle = Normal diet group, black squares = High-fat diet group. Data are mean ± SEM (n = 6), *p<0.05, **p<0.01, ***p<0.001.

Mentions: C57BL/6J mice were fed HFD and ND respectively. At 22 weeks, body weight of mice fed HFD was significantly increased (35.5±0.99 g) as compared to the ND group (24.5 ± 0.39 g) (Table 1; Fig. 2A), and gonadal WAT weight of HFD group per body weight was significantly higher than that of ND group (Table 1). However, the interscapular BAT weight of HFD group per body weight was significantly lower than that of ND group (Table 1). The plasma levels of TC and TG were strongly higher in HFD group (Table 1).


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)

Body weight and metabolic status of mice were affected by HFD.HFD significantly altered the body weight (A), and induced glucose intolerance (B) in C57BL/6J mice. Black circle = Normal diet group, black squares = High-fat diet group. Data are mean ± SEM (n = 6), *p<0.05, **p<0.01, ***p<0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0119350.g002: Body weight and metabolic status of mice were affected by HFD.HFD significantly altered the body weight (A), and induced glucose intolerance (B) in C57BL/6J mice. Black circle = Normal diet group, black squares = High-fat diet group. Data are mean ± SEM (n = 6), *p<0.05, **p<0.01, ***p<0.001.
Mentions: C57BL/6J mice were fed HFD and ND respectively. At 22 weeks, body weight of mice fed HFD was significantly increased (35.5±0.99 g) as compared to the ND group (24.5 ± 0.39 g) (Table 1; Fig. 2A), and gonadal WAT weight of HFD group per body weight was significantly higher than that of ND group (Table 1). However, the interscapular BAT weight of HFD group per body weight was significantly lower than that of ND group (Table 1). The plasma levels of TC and TG were strongly higher in HFD group (Table 1).

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