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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

B1B2KO mice have low insulin and leptin levels.Notes: (A) Serum leptin levels after 12 weeks of HFD treatment. (B) Serum insulin levels after 12 weeks of HFD treatment. (C) Leptin mRNA expression in white adipose tissue after 12 weeks of HFD treatment. White bars indicate WT control and HFD, and black bars indicate B1B2KO control and HFD. *P<0.05 B1B2KO control versus WT control; **P<0.01 B1B2KO HFD versus WT HFD; #P<0.05 WT HFD versus WT control. (D) Leptin sensitivity test in WT and B1B2KO mice. Consumption was measured after intraperitoneal injection of 40 µg/day of leptin and compared with basal consumption. Data are expressed as the mean ± standard error of the mean and represent percentage of food intake. White squares indicate WT, black squares indicate B1B2KO. (E) Insulin sensitivity test after 12 weeks of HFD treatment. Glycemia was measured before and after intraperitoneal injection of insulin 0.01 U/kg at following the times: 0, 15, 30, and 60 minutes. Data are expressed as the mean ± standard error of the mean. White circles indicate WT control, black circles indicate WT HFD, white triangles indicate B1B2KO control, and black triangles indicate B1B2KO HFD. *P<0.05 WT HFD versus all groups.Abbreviations: HFD, high-fat diet; WT, wild-type.
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f3-dmso-8-399: B1B2KO mice have low insulin and leptin levels.Notes: (A) Serum leptin levels after 12 weeks of HFD treatment. (B) Serum insulin levels after 12 weeks of HFD treatment. (C) Leptin mRNA expression in white adipose tissue after 12 weeks of HFD treatment. White bars indicate WT control and HFD, and black bars indicate B1B2KO control and HFD. *P<0.05 B1B2KO control versus WT control; **P<0.01 B1B2KO HFD versus WT HFD; #P<0.05 WT HFD versus WT control. (D) Leptin sensitivity test in WT and B1B2KO mice. Consumption was measured after intraperitoneal injection of 40 µg/day of leptin and compared with basal consumption. Data are expressed as the mean ± standard error of the mean and represent percentage of food intake. White squares indicate WT, black squares indicate B1B2KO. (E) Insulin sensitivity test after 12 weeks of HFD treatment. Glycemia was measured before and after intraperitoneal injection of insulin 0.01 U/kg at following the times: 0, 15, 30, and 60 minutes. Data are expressed as the mean ± standard error of the mean. White circles indicate WT control, black circles indicate WT HFD, white triangles indicate B1B2KO control, and black triangles indicate B1B2KO HFD. *P<0.05 WT HFD versus all groups.Abbreviations: HFD, high-fat diet; WT, wild-type.

Mentions: In order to better understand the metabolic profile in B1B2KO mice, we measured two important hormones involved in energy homeostasis, ie, insulin and leptin. Insulin and leptin levels (protein in the serum and mRNA from white adipose tissue) were decreased in B1B2KO mice when compared with WT mice using both regimens (Figure 3A–C). No difference in leptin sensitivity was observed in B1B2KO mice after the HFD (Figure 3D). Also, B1B2KO mice on the control diet or HFD did not present changes in insulin sensitivity when compared with WT mice (Figure 3E).


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)

B1B2KO mice have low insulin and leptin levels.Notes: (A) Serum leptin levels after 12 weeks of HFD treatment. (B) Serum insulin levels after 12 weeks of HFD treatment. (C) Leptin mRNA expression in white adipose tissue after 12 weeks of HFD treatment. White bars indicate WT control and HFD, and black bars indicate B1B2KO control and HFD. *P<0.05 B1B2KO control versus WT control; **P<0.01 B1B2KO HFD versus WT HFD; #P<0.05 WT HFD versus WT control. (D) Leptin sensitivity test in WT and B1B2KO mice. Consumption was measured after intraperitoneal injection of 40 µg/day of leptin and compared with basal consumption. Data are expressed as the mean ± standard error of the mean and represent percentage of food intake. White squares indicate WT, black squares indicate B1B2KO. (E) Insulin sensitivity test after 12 weeks of HFD treatment. Glycemia was measured before and after intraperitoneal injection of insulin 0.01 U/kg at following the times: 0, 15, 30, and 60 minutes. Data are expressed as the mean ± standard error of the mean. White circles indicate WT control, black circles indicate WT HFD, white triangles indicate B1B2KO control, and black triangles indicate B1B2KO HFD. *P<0.05 WT HFD versus all groups.Abbreviations: HFD, high-fat diet; WT, wild-type.
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f3-dmso-8-399: B1B2KO mice have low insulin and leptin levels.Notes: (A) Serum leptin levels after 12 weeks of HFD treatment. (B) Serum insulin levels after 12 weeks of HFD treatment. (C) Leptin mRNA expression in white adipose tissue after 12 weeks of HFD treatment. White bars indicate WT control and HFD, and black bars indicate B1B2KO control and HFD. *P<0.05 B1B2KO control versus WT control; **P<0.01 B1B2KO HFD versus WT HFD; #P<0.05 WT HFD versus WT control. (D) Leptin sensitivity test in WT and B1B2KO mice. Consumption was measured after intraperitoneal injection of 40 µg/day of leptin and compared with basal consumption. Data are expressed as the mean ± standard error of the mean and represent percentage of food intake. White squares indicate WT, black squares indicate B1B2KO. (E) Insulin sensitivity test after 12 weeks of HFD treatment. Glycemia was measured before and after intraperitoneal injection of insulin 0.01 U/kg at following the times: 0, 15, 30, and 60 minutes. Data are expressed as the mean ± standard error of the mean. White circles indicate WT control, black circles indicate WT HFD, white triangles indicate B1B2KO control, and black triangles indicate B1B2KO HFD. *P<0.05 WT HFD versus all groups.Abbreviations: HFD, high-fat diet; WT, wild-type.
Mentions: In order to better understand the metabolic profile in B1B2KO mice, we measured two important hormones involved in energy homeostasis, ie, insulin and leptin. Insulin and leptin levels (protein in the serum and mRNA from white adipose tissue) were decreased in B1B2KO mice when compared with WT mice using both regimens (Figure 3A–C). No difference in leptin sensitivity was observed in B1B2KO mice after the HFD (Figure 3D). Also, B1B2KO mice on the control diet or HFD did not present changes in insulin sensitivity when compared with WT mice (Figure 3E).

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