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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 are protected against obesity induced by HFD treatment and present lower food intake and feed efficiency.Notes: (A) Body weight after 12 weeks of HFD treatment. *P<0.05 WT HFD versus B1B2KO groups; #P<0.05 versus all groups. Data are expressed as the mean ± standard error of the mean and represent mouse weight per gram. White circles indicate WT control, black circles indicate WT HFD, white triangles indicate B1B2KO control, and black triangles indicate B1B2KO HFD. (B) Visceral fat weight after 12 weeks of HFD treatment. White bars indicate WT control and HFD, and black bars indicate B1B2KO control and HFD. #P<0.05 WT HFD versus WT control; **P<0.01 WT HFD versus B1B2KO HFD. Data are expressed as the mean ± standard error of the mean and represent visceral fat depot weight per gram. (C) Energy intake after 12 weeks of HFD treatment. Energy intake was calculated based on information from the chow manufacturer. 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 B1B2KO HFD; #P<0.05 WT control versus B1B2KO control. Data are expressed as the mean ± standard error of the mean and represent energy intake (kCal). (D) Cumulative food intake after 12 weeks of HFD treatment. White bars indicate WT control and HFD, black bars indicate B1B2KO control and HFD. *P<0.05 WT control versus B1B2KO control; #P<0.05 WT HFD versus B1B2KO HFD. Data are expressed as the mean ± standard error of the mean and represent chow per gram. (E) Feed efficiency after 12 weeks of HFD treatment. Feed efficiency was calculated by the ratio of total weight gain and calories of food ingested after the HFD treatment in both WT and B1B2KO mice. White bars indicate WT control and HFD, black bars indicate B1B2KO control and HFD. P<0.01 WT HFD versus control diet group. **P<0.01 WT HFD versus B1B2KO HFD. Data are expressed as the mean ± standard error of the mean and represent energy intake (kCal).Abbreviations: HFD, high-fat diet; WT, wild-type.
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f2-dmso-8-399: B1B2KO mice are protected against obesity induced by HFD treatment and present lower food intake and feed efficiency.Notes: (A) Body weight after 12 weeks of HFD treatment. *P<0.05 WT HFD versus B1B2KO groups; #P<0.05 versus all groups. Data are expressed as the mean ± standard error of the mean and represent mouse weight per gram. White circles indicate WT control, black circles indicate WT HFD, white triangles indicate B1B2KO control, and black triangles indicate B1B2KO HFD. (B) Visceral fat weight after 12 weeks of HFD treatment. White bars indicate WT control and HFD, and black bars indicate B1B2KO control and HFD. #P<0.05 WT HFD versus WT control; **P<0.01 WT HFD versus B1B2KO HFD. Data are expressed as the mean ± standard error of the mean and represent visceral fat depot weight per gram. (C) Energy intake after 12 weeks of HFD treatment. Energy intake was calculated based on information from the chow manufacturer. 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 B1B2KO HFD; #P<0.05 WT control versus B1B2KO control. Data are expressed as the mean ± standard error of the mean and represent energy intake (kCal). (D) Cumulative food intake after 12 weeks of HFD treatment. White bars indicate WT control and HFD, black bars indicate B1B2KO control and HFD. *P<0.05 WT control versus B1B2KO control; #P<0.05 WT HFD versus B1B2KO HFD. Data are expressed as the mean ± standard error of the mean and represent chow per gram. (E) Feed efficiency after 12 weeks of HFD treatment. Feed efficiency was calculated by the ratio of total weight gain and calories of food ingested after the HFD treatment in both WT and B1B2KO mice. White bars indicate WT control and HFD, black bars indicate B1B2KO control and HFD. P<0.01 WT HFD versus control diet group. **P<0.01 WT HFD versus B1B2KO HFD. Data are expressed as the mean ± standard error of the mean and represent energy intake (kCal).Abbreviations: HFD, high-fat diet; WT, wild-type.

Mentions: Body weight was measured for 12 weeks in B1B2KO mice on a control diet or the HFD. The mice had a reduced body weight and smaller visceral fat depots after the HFD but not after the control diet (Figure 2A and B). To investigate why B1B2KO mice were protected against HFD-induced weight gain, food and energy intake was measured every week during the HFD and chow diet regimen. As shown in Figure 2C and D, WT mice showed higher food intake and calories ingested when compared with B1B2KO mice regardless of the type of diet. Also, the B1B2KO mice on the HFD showed lower feeding efficiency (Figure 2E), indicating more energy expenditure after the HFD.


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 are protected against obesity induced by HFD treatment and present lower food intake and feed efficiency.Notes: (A) Body weight after 12 weeks of HFD treatment. *P<0.05 WT HFD versus B1B2KO groups; #P<0.05 versus all groups. Data are expressed as the mean ± standard error of the mean and represent mouse weight per gram. White circles indicate WT control, black circles indicate WT HFD, white triangles indicate B1B2KO control, and black triangles indicate B1B2KO HFD. (B) Visceral fat weight after 12 weeks of HFD treatment. White bars indicate WT control and HFD, and black bars indicate B1B2KO control and HFD. #P<0.05 WT HFD versus WT control; **P<0.01 WT HFD versus B1B2KO HFD. Data are expressed as the mean ± standard error of the mean and represent visceral fat depot weight per gram. (C) Energy intake after 12 weeks of HFD treatment. Energy intake was calculated based on information from the chow manufacturer. 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 B1B2KO HFD; #P<0.05 WT control versus B1B2KO control. Data are expressed as the mean ± standard error of the mean and represent energy intake (kCal). (D) Cumulative food intake after 12 weeks of HFD treatment. White bars indicate WT control and HFD, black bars indicate B1B2KO control and HFD. *P<0.05 WT control versus B1B2KO control; #P<0.05 WT HFD versus B1B2KO HFD. Data are expressed as the mean ± standard error of the mean and represent chow per gram. (E) Feed efficiency after 12 weeks of HFD treatment. Feed efficiency was calculated by the ratio of total weight gain and calories of food ingested after the HFD treatment in both WT and B1B2KO mice. White bars indicate WT control and HFD, black bars indicate B1B2KO control and HFD. P<0.01 WT HFD versus control diet group. **P<0.01 WT HFD versus B1B2KO HFD. Data are expressed as the mean ± standard error of the mean and represent energy intake (kCal).Abbreviations: HFD, high-fat diet; WT, wild-type.
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f2-dmso-8-399: B1B2KO mice are protected against obesity induced by HFD treatment and present lower food intake and feed efficiency.Notes: (A) Body weight after 12 weeks of HFD treatment. *P<0.05 WT HFD versus B1B2KO groups; #P<0.05 versus all groups. Data are expressed as the mean ± standard error of the mean and represent mouse weight per gram. White circles indicate WT control, black circles indicate WT HFD, white triangles indicate B1B2KO control, and black triangles indicate B1B2KO HFD. (B) Visceral fat weight after 12 weeks of HFD treatment. White bars indicate WT control and HFD, and black bars indicate B1B2KO control and HFD. #P<0.05 WT HFD versus WT control; **P<0.01 WT HFD versus B1B2KO HFD. Data are expressed as the mean ± standard error of the mean and represent visceral fat depot weight per gram. (C) Energy intake after 12 weeks of HFD treatment. Energy intake was calculated based on information from the chow manufacturer. 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 B1B2KO HFD; #P<0.05 WT control versus B1B2KO control. Data are expressed as the mean ± standard error of the mean and represent energy intake (kCal). (D) Cumulative food intake after 12 weeks of HFD treatment. White bars indicate WT control and HFD, black bars indicate B1B2KO control and HFD. *P<0.05 WT control versus B1B2KO control; #P<0.05 WT HFD versus B1B2KO HFD. Data are expressed as the mean ± standard error of the mean and represent chow per gram. (E) Feed efficiency after 12 weeks of HFD treatment. Feed efficiency was calculated by the ratio of total weight gain and calories of food ingested after the HFD treatment in both WT and B1B2KO mice. White bars indicate WT control and HFD, black bars indicate B1B2KO control and HFD. P<0.01 WT HFD versus control diet group. **P<0.01 WT HFD versus B1B2KO HFD. Data are expressed as the mean ± standard error of the mean and represent energy intake (kCal).Abbreviations: HFD, high-fat diet; WT, wild-type.
Mentions: Body weight was measured for 12 weeks in B1B2KO mice on a control diet or the HFD. The mice had a reduced body weight and smaller visceral fat depots after the HFD but not after the control diet (Figure 2A and B). To investigate why B1B2KO mice were protected against HFD-induced weight gain, food and energy intake was measured every week during the HFD and chow diet regimen. As shown in Figure 2C and D, WT mice showed higher food intake and calories ingested when compared with B1B2KO mice regardless of the type of diet. Also, the B1B2KO mice on the HFD showed lower feeding efficiency (Figure 2E), indicating more energy expenditure after the HFD.

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