Original Article

International Journal of Obesity (2008) 32, 936–942; doi:10.1038/ijo.2008.13; published online 19 February 2008

Effects of leptin on energy metabolism in bold beta-less mice

C S Asensio1,2, D Arsenijevic2, L Lehr3, J-P Giacobino3, P Muzzin1 and F Rohner-Jeanrenaud2

  1. 1Department of Cell Physiology and Metabolism, Medical University Centre, Geneva, Switzerland
  2. 2Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, Medical University Centre, Geneva, Switzerland
  3. 3Department of Medical Biochemistry, Medical University Centre, Geneva, Switzerland

Correspondence: Dr CS Asensio, Department of Neurology, University of California, San Francisco, 600 16th Street, Genentech Hall, N274, San Francisco, CA 94158, USA. E-mail: Cedric.Asensio@ucsf.edu

Received 22 July 2007; Revised 7 January 2008; Accepted 15 January 2008; Published online 19 February 2008.

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Abstract

Objective:

 

To investigate the impact of beta-adrenoceptor deficiency on the metabolic effects of leptin.

Measurements:

 

Leptin was infused subcutaneously through an osmotic minipump in wild-type (WT) and beta1/beta2/beta3-adrenoceptor knockout (beta-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 beta-less mice. In pair-fed animals being used as controls, leptin treatment was found to increase energy expenditure in WT, but not in beta-less mice. No difference was observed in carbohydrate or fat utilization between leptin-treated WT and beta-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 beta-less mouse BAT.

Conclusion:

 

The stimulatory effects of leptin on oxygen consumption, BAT UCP1 and D2 expression require functional beta-adrenoceptors, but its inhibitory effect on food intake and its stimulatory effect on fat utilization is independent of the beta-adrenoceptor signalling.

Keywords:

leptin, beta-adrenoceptor knockout mice, energy expenditure, brown adipose tissue, thermogenic markers

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