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
Institution
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
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