Kinin B1 receptor deficiency leads to leptin hypersensitivity and resistance to obesity.
OBJECTIVE
Kinins mediate pathophysiological processes related to hypertension, pain, and inflammation through the activation of two G-protein-coupled receptors, named B(1) and B(2). Although these peptides have been related to glucose homeostasis, their effects on energy balance are still unknown.


METHODS
Using genetic and pharmacological strategies to abrogate the kinin B(1) receptor in different animal models of obesity, here we present evidence of a novel role for kinins in the regulation of satiety and adiposity.


RESULTS
Kinin B(1) receptor deficiency in mice (B(1)(-/-)) resulted in less fat content, hypoleptinemia, increased leptin sensitivity, and robust protection against high-fat diet-induced weight gain. Under high-fat diet, B(1)(-/-) also exhibited reduced food intake, improved lipid oxidation, and increased energy expenditure. Surprisingly, B(1) receptor deficiency was not able to decrease food intake and adiposity in obese mice lacking leptin (ob/ob-B(1)(-/-)). However, ob/ob-B(1)(-/-) mice were more responsive to the effects of exogenous leptin on body weight and food intake, suggesting that B(1) receptors may be dependent on leptin to display their metabolic roles. Finally, inhibition of weight gain and food intake by B(1) receptor ablation was pharmacologically confirmed by long-term administration of the kinin B(1) receptor antagonist SSR240612 to mice under high-fat diet.


CONCLUSIONS
Our data suggest that kinin B(1) receptors participate in the regulation of the energy balance via a mechanism that could involve the modulation of leptin sensitivity.
Mori
Marcelo A
MA
Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil.
Araújo
Ronaldo C
RC
Reis
Felipe C G
FC
Sgai
Daniela G
DG
Fonseca
Raphael G
RG
Barros
Carlos C
CC
Merino
Vanessa F
VF
Passadore
Mariana
M
Barbosa
Ana M
AM
Ferrari
Bernard
B
Carayon
Pierre
P
Castro
Charlles H M
CH
Shimuta
Suma I
SI
Luz
Jacqueline
J
Bascands
Jean-Loup
JL
Schanstra
Joost P
JP
Even
Patrick C
PC
Oliveira
Suzana M
SM
Bader
Michael
M
Pesquero
João B
JB
D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D001823:Body Composition; D002153:Calorimetry, Indirect; D004041:Dietary Fats; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000517:prevention & control*; D043783:Receptor, Bradykinin B1 / Q000172:deficiency*
D004041:Dietary Fats; D020738:Leptin; D043783:Receptor, Bradykinin B1