Abstract

Beta 3-adrenergic receptors (B3-AR) are thought to play an important role in regulating energy expenditure and B3-selective agonists are being developed as anti-obesity drugs. A number of unresolved issues persist regarding the potential of this receptor as an anti-obesity target. Knockout mice lacking B3-AR have been generated in the previous grant period. The present application proposed to 1) use mice lacking B3-ARs to assess the role of B3-ARs in regulating energy balance: influence of diet and background genes 2) to assess effects of genetically altered a2-AR/B3AR ratios or the Trp64Arg human B3-AR variant on adrenergic signalling in adipocytes; 3) to determine the molecular basis for selective expression of human B3-ARs in brown adipocytes; 4) to use mice lacking B3-AR to establish the existence of additional atypical B-ARs and to molecularly clone and characterize these novel receptors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK049569-05
Application #
2905729
Study Section
Nutrition Study Section (NTN)
Program Officer
Yanovski, Susan Z
Project Start
1995-05-30
Project End
2003-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Vianna, Claudia R; Huntgeburth, Michael; Coppari, Roberto et al. (2006) Hypomorphic mutation of PGC-1beta causes mitochondrial dysfunction and liver insulin resistance. Cell Metab 4:453-64
Huppertz, C; Fischer, B M; Kim, Y B et al. (2001) Uncoupling protein 3 (UCP3) stimulates glucose uptake in muscle cells through a phosphoinositide 3-kinase-dependent mechanism. J Biol Chem 276:12520-9
Vidal-Puig, A J; Grujic, D; Zhang, C Y et al. (2000) Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem 275:16258-66
Cohen, M L; Bloomquist, W; Ito, M et al. (2000) Beta3 receptors mediate relaxation in stomach fundus whereas a fourth beta receptor mediates tachycardia in atria from transgenic beta3 receptor knockout mice. Receptors Channels 7:17-23
Hagen, T; Lowell, B B (2000) Chimeric proteins between UCP1 and UCP3: the middle third of UCP1 is necessary and sufficient for activation by fatty acids. Biochem Biophys Res Commun 276:642-8
Hagen, T; Zhang, C Y; Vianna, C R et al. (2000) Uncoupling proteins 1 and 3 are regulated differently. Biochemistry 39:5845-51
Zhang, C Y; Hagen, T; Mootha, V K et al. (1999) Assessment of uncoupling activity of uncoupling protein 3 using a yeast heterologous expression system. FEBS Lett 449:129-34
Hagen, T; Zhang, C Y; Slieker, L J et al. (1999) Assessment of uncoupling activity of the human uncoupling protein 3 short form and three mutants of the uncoupling protein gene using a yeast heterologous expression system. FEBS Lett 454:201-6
Vidal-Puig, A; Rosenbaum, M; Considine, R C et al. (1999) Effects of obesity and stable weight reduction on UCP2 and UCP3 gene expression in humans. Obes Res 7:133-40
Boss, O; Bachman, E; Vidal-Puig, A et al. (1999) Role of the beta(3)-adrenergic receptor and/or a putative beta(4)-adrenergic receptor on the expression of uncoupling proteins and peroxisome proliferator-activated receptor-gamma coactivator-1. Biochem Biophys Res Commun 261:870-6

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