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Research Article Free access | 10.1172/JCI119620

Targeted gene disruption reveals a leptin-independent role for the mouse beta3-adrenoceptor in the regulation of body composition.

J P Revelli, F Preitner, S Samec, P Muniesa, F Kuehne, O Boss, J D Vassalli, A Dulloo, J Seydoux, J P Giacobino, J Huarte, and C Ody

Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland.

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Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland.

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Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland.

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Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland.

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Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland.

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Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland.

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Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland.

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Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland.

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Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland.

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Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland.

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Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland.

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Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland.

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Published September 1, 1997 - More info

Published in Volume 100, Issue 5 on September 1, 1997
J Clin Invest. 1997;100(5):1098–1106. https://doi.org/10.1172/JCI119620.
© 1997 The American Society for Clinical Investigation
Published September 1, 1997 - Version history
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Abstract

Targeted disruption of mouse beta3-adrenoceptor was generated by homologous recombination, and validated by an acute in vivo study showing a complete lack of effect of the beta3-adrenoceptor agonist CL 316,243 on the metabolic rate of homozygous null (-/-) mice. In brown adipose tissue, beta3-adrenoceptor disruption induced a 66% decrease (P < 0.005) in beta1-adrenoceptor mRNA level, whereas leptin mRNA remained unchanged. Chronic energy balance studies in chow-fed mice showed that in -/- mice, body fat accumulation was favored (+41%, P < 0.01), with a slight increase in food intake (+6%, NS). These effects were accentuated by high fat feeding: -/- mice showed increased total body fat (+56%, P < 0.025) and food intake (+12%, P < 0.01), and a decrease in the fat-free dry mass (-10%, P < 0.05), which reflects a reduction in body protein content. Circulating leptin levels were not different in -/- and control mice regardless of diet. The significant shift to the right in the positive correlation between circulating leptin and percentage of body fat in high fat-fed -/- mice suggests that the threshold of body fat content inducing leptin secretion is higher in -/- than in control mice. Taken together, these studies demonstrate that beta3-adrenoceptor disruption creates conditions which predispose to the development of obesity.

Version history
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