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Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice.

Morais RL, Silva ED, Sales VM, Filippelli-Silva R, Mori MA, Bader M, Pesquero JB - Diabetes Metab Syndr Obes (2015)

Bottom Line: The kallikrein-kinin system is well known for its role in pain and inflammation, and has been shown recently by our group to have a role also in the regulation of energy expenditure.However, it is also known that in the absence of B1 receptor, the B2 receptor is overexpressed and can take over the function of its B1 counterpart, rendering uncertain the role of each kinin receptor in these metabolic effects.They also had lower blood insulin and leptin levels and higher glucose tolerance after treatment with an HFD.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil.

ABSTRACT
The kallikrein-kinin system is well known for its role in pain and inflammation, and has been shown recently by our group to have a role also in the regulation of energy expenditure. We have demonstrated that B1 receptor knockout (B1KO) mice are resistant to obesity induced by a high-fat diet (HFD) and that B1 receptor expression in adipocytes regulates glucose tolerance and predisposition to obesity. However, it is also known that in the absence of B1 receptor, the B2 receptor is overexpressed and can take over the function of its B1 counterpart, rendering uncertain the role of each kinin receptor in these metabolic effects. Therefore, we investigated the impact of ablation of each kinin receptor on energy metabolism using double kinin receptor knockout (B1B2KO) mice. Our data show that B1B2KO mice were resistant to HFD-induced obesity, with lower food intake and feed efficiency when compared with wild-type mice. They also had lower blood insulin and leptin levels and higher glucose tolerance after treatment with an HFD. Gene expression for tumor necrosis factor-alpha and C-reactive protein, which are important genes for insulin resistance, was reduced in white adipose tissue, skeletal muscle, and the liver in B1B2KO mice after the HFD. In summary, our data show that disruption of kinin B1 and B2 receptors has a profound impact on metabolic homeostasis in mice, by improving glucose tolerance and preventing HFD-induced obesity. These novel findings could pave the way for development of new pharmacological strategies to treat metabolic disorders such as insulin resistance and obesity.

No MeSH data available.


Related in: MedlinePlus

Inflammatory cytokines are downregulated in tissues of B1B2KO mice.Notes: TNF-α mRNA expression in white adipose tissue (A) and skeletal muscle tissue (B) after 12 weeks of HFD treatment. (C) CRP mRNA expression in the liver after 12 weeks of HFD treatment. Data are expressed as the mean ± standard error of the mean of the 2−ΔCt parameter and represent the relative expression between TNF-α/CRP and β-actin. White bars indicate WT control and HFD, black bars indicate B1B2KO control and HFD. *P<0.05 B1B2KO HFD versus WT HFD.Abbreviations: HFD, high-fat diet; WT, wild-type; CRP, C-reactive protein; TNF-α, tumor necrosis factor-alpha.
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f5-dmso-8-399: Inflammatory cytokines are downregulated in tissues of B1B2KO mice.Notes: TNF-α mRNA expression in white adipose tissue (A) and skeletal muscle tissue (B) after 12 weeks of HFD treatment. (C) CRP mRNA expression in the liver after 12 weeks of HFD treatment. Data are expressed as the mean ± standard error of the mean of the 2−ΔCt parameter and represent the relative expression between TNF-α/CRP and β-actin. White bars indicate WT control and HFD, black bars indicate B1B2KO control and HFD. *P<0.05 B1B2KO HFD versus WT HFD.Abbreviations: HFD, high-fat diet; WT, wild-type; CRP, C-reactive protein; TNF-α, tumor necrosis factor-alpha.

Mentions: Given the importance of inflammation in the pathogenesis of insulin resistance, we measured the expression of two inflammatory mediators in different metabolic tissues of double knockout mice. TNF-α mRNA expression was reduced in both white adipose tissue and skeletal muscle in B1B2KO mice after the HFD (Figure 5A and B). Similarly, CRP mRNA expression was decreased in the livers of the B1B2KO mice after the HFD (Figure 5C). In addition, WT mice were treated for 7 days with specific B1 (R-715) and B2 (HOE-140) receptor antagonists. Gene expression of leptin and TNF-α in white adipose tissue and skeletal muscle was measured and CRP expression was evaluated in the liver, but no differences were observed (data not shown).


Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice.

Morais RL, Silva ED, Sales VM, Filippelli-Silva R, Mori MA, Bader M, Pesquero JB - Diabetes Metab Syndr Obes (2015)

Inflammatory cytokines are downregulated in tissues of B1B2KO mice.Notes: TNF-α mRNA expression in white adipose tissue (A) and skeletal muscle tissue (B) after 12 weeks of HFD treatment. (C) CRP mRNA expression in the liver after 12 weeks of HFD treatment. Data are expressed as the mean ± standard error of the mean of the 2−ΔCt parameter and represent the relative expression between TNF-α/CRP and β-actin. White bars indicate WT control and HFD, black bars indicate B1B2KO control and HFD. *P<0.05 B1B2KO HFD versus WT HFD.Abbreviations: HFD, high-fat diet; WT, wild-type; CRP, C-reactive protein; TNF-α, tumor necrosis factor-alpha.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554409&req=5

f5-dmso-8-399: Inflammatory cytokines are downregulated in tissues of B1B2KO mice.Notes: TNF-α mRNA expression in white adipose tissue (A) and skeletal muscle tissue (B) after 12 weeks of HFD treatment. (C) CRP mRNA expression in the liver after 12 weeks of HFD treatment. Data are expressed as the mean ± standard error of the mean of the 2−ΔCt parameter and represent the relative expression between TNF-α/CRP and β-actin. White bars indicate WT control and HFD, black bars indicate B1B2KO control and HFD. *P<0.05 B1B2KO HFD versus WT HFD.Abbreviations: HFD, high-fat diet; WT, wild-type; CRP, C-reactive protein; TNF-α, tumor necrosis factor-alpha.
Mentions: Given the importance of inflammation in the pathogenesis of insulin resistance, we measured the expression of two inflammatory mediators in different metabolic tissues of double knockout mice. TNF-α mRNA expression was reduced in both white adipose tissue and skeletal muscle in B1B2KO mice after the HFD (Figure 5A and B). Similarly, CRP mRNA expression was decreased in the livers of the B1B2KO mice after the HFD (Figure 5C). In addition, WT mice were treated for 7 days with specific B1 (R-715) and B2 (HOE-140) receptor antagonists. Gene expression of leptin and TNF-α in white adipose tissue and skeletal muscle was measured and CRP expression was evaluated in the liver, but no differences were observed (data not shown).

Bottom Line: The kallikrein-kinin system is well known for its role in pain and inflammation, and has been shown recently by our group to have a role also in the regulation of energy expenditure.However, it is also known that in the absence of B1 receptor, the B2 receptor is overexpressed and can take over the function of its B1 counterpart, rendering uncertain the role of each kinin receptor in these metabolic effects.They also had lower blood insulin and leptin levels and higher glucose tolerance after treatment with an HFD.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil.

ABSTRACT
The kallikrein-kinin system is well known for its role in pain and inflammation, and has been shown recently by our group to have a role also in the regulation of energy expenditure. We have demonstrated that B1 receptor knockout (B1KO) mice are resistant to obesity induced by a high-fat diet (HFD) and that B1 receptor expression in adipocytes regulates glucose tolerance and predisposition to obesity. However, it is also known that in the absence of B1 receptor, the B2 receptor is overexpressed and can take over the function of its B1 counterpart, rendering uncertain the role of each kinin receptor in these metabolic effects. Therefore, we investigated the impact of ablation of each kinin receptor on energy metabolism using double kinin receptor knockout (B1B2KO) mice. Our data show that B1B2KO mice were resistant to HFD-induced obesity, with lower food intake and feed efficiency when compared with wild-type mice. They also had lower blood insulin and leptin levels and higher glucose tolerance after treatment with an HFD. Gene expression for tumor necrosis factor-alpha and C-reactive protein, which are important genes for insulin resistance, was reduced in white adipose tissue, skeletal muscle, and the liver in B1B2KO mice after the HFD. In summary, our data show that disruption of kinin B1 and B2 receptors has a profound impact on metabolic homeostasis in mice, by improving glucose tolerance and preventing HFD-induced obesity. These novel findings could pave the way for development of new pharmacological strategies to treat metabolic disorders such as insulin resistance and obesity.

No MeSH data available.


Related in: MedlinePlus