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

Details

Serval ID
serval:BIB_40CED56E402D
Type
Article: article from journal or magazin.
Collection
Publications
Title
Targeted gene disruption reveals a leptin-independent role for the mouse beta3-adrenoceptor in the regulation of body composition.
Journal
Journal of Clinical Investigation
Author(s)
Revelli J.P., Preitner F., Samec S., Muniesa P., Kuehne F., Boss O., Vassalli J.D., Dulloo A., Seydoux J., Giacobino J.P., Huarte J., Ody C.
ISSN
0021-9738 (Print)
ISSN-L
0021-9738
Publication state
Published
Issued date
1997
Volume
100
Number
5
Pages
1098-1106
Language
english
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.
Keywords
Adipose Tissue/physiology, Animals, Blotting, Northern, Body Composition, Body Temperature Regulation, Cells, Cultured, Dietary Fats/administration & dosage, Energy Metabolism, Leptin, Male, Mice, Proteins/analysis, Proteins/physiology, Receptors, Adrenergic, beta/genetics, Receptors, Adrenergic, beta/physiology, Receptors, Adrenergic, beta-1/physiology, Receptors, Adrenergic, beta-3, Receptors, Leptin
Pubmed
Web of science
Open Access
Yes
Create date
18/12/2012 15:50
Last modification date
20/08/2019 13:39
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