Kinin B sub(1) 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 sub(1) and B sub(2). Although these peptides have been related to glucose homeostasis, their effects on energy balance are still u...
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Published in | Diabetes (New York, N.Y.) Vol. 57; no. 6; pp. 1491 - 1500 |
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Main Authors | , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.06.2008
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Online Access | Get full text |
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Summary: | OBJECTIVE:-Kinins mediate pathophysiological processes related to hypertension, pain, and inflammation through the activation of two G-protein-coupled receptors, named B sub(1) and B sub(2). Although these peptides have been related to glucose homeostasis, their effects on energy balance are still unknown. RESEARCH DESIGN AND METHODS-Using genetic and pharmacological strategies to abrogate the kinin B sub(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 sub(1) receptor deficiency in mice (B sub(1) super(-/-)) resulted in less fat content, hypoleptinemia, increased leptin sensitivity, and robust protection against high-fat diet-induced weight gain. Under high-fat diet, B sub(1) super(-/-) also exhibited reduced food intake, improved lipid oxidation, and increased energy expenditure. Surprisingly, B sub(1) receptor deficiency was not able to decrease food intake and adiposity in obese mice lacking leptin (ob/ob-B sub(1) super(-/-)). However, ob/ob-B sub(1) super(-/-) mice were more responsive to the effects of exogenous leptin on body weight and food intake, suggesting that B sub(1) receptors may be dependent on leptin to display their metabolic roles. Finally, inhibition of weight gain and food intake by B sub(1) receptor ablation was pharmacologically confirmed by long-term administration of the kinin B sub(1) receptor antagonist SSR240612 to mice under high-fat diet. CONCLUSIONS:-Our data suggest that kinin B sub(1) receptors participate in the regulation of the energy balance via a mechanism that could involve the modulation of leptin sensitivity. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-2 |
ISSN: | 0012-1797 |