Abstract
Objective:
To investigate the impact of β-adrenoceptor deficiency on the metabolic effects of leptin.
Measurements:
Leptin was infused subcutaneously through an osmotic minipump in wild-type (WT) and β1/β2/β3-adrenoceptor knockout (β-less) mice and its effects on food intake, energy expenditure, carbohydrate and lipid utilization as well as on the levels of expression of the brown adipose tissue (BAT), thermogenic marker uncoupling protein-1 (UCP1) and type II deiodinase (D2) mRNAs were compared.
Results:
Leptin treatment decreased food intake by 23% in both the WT and the β-less mice. In pair-fed animals being used as controls, leptin treatment was found to increase energy expenditure in WT, but not in β-less mice. No difference was observed in carbohydrate or fat utilization between leptin-treated WT and β-less mice. Leptin increased UCP1 and D2 mRNA levels in WT mouse BAT 1.7- and 3-fold, respectively, but had no effect on the expression of these genes in β-less mouse BAT.
Conclusion:
The stimulatory effects of leptin on oxygen consumption, BAT UCP1 and D2 expression require functional β-adrenoceptors, but its inhibitory effect on food intake and its stimulatory effect on fat utilization is independent of the β-adrenoceptor signalling.
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Acknowledgements
This study was funded by the Swiss National Science Foundation Grants no. 3100AO-105889 (to FRJ), the Fondation Boninchi (to PM), the Fondation du Centenaire de la Société suisse d’Assurances générales sur la vie humaine pour la santé publique et les recherches médicales (to PM) and the European Community (EC) FP6 funding (to FRJ), contract no. LSHM-CT-2003-503041. This study was part of the Geneva Programme for Metabolic Disorders. We are very grateful to Dr Kobilka for providing us with the double KO mice. Finally, we thank Ms Marcella Klein for her excellent technical assistance.
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Asensio, C., Arsenijevic, D., Lehr, L. et al. Effects of leptin on energy metabolism in β-less mice. Int J Obes 32, 936–942 (2008). https://doi.org/10.1038/ijo.2008.13
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DOI: https://doi.org/10.1038/ijo.2008.13
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