The research proposed herein will investigate the cellular mechanisms which underlie the regulation of thermogenesis in hamster brown adipocytes. Thermogenesis in brown fat cells is subject to bimodal regulation: stimulation by catecholamines acting via both beta and alpha-1 adrenergic receptors and inhibition by adenosine, acting via A1 type receptors. Adenosine is capable of antagonizing the thermogenic response to both beta or alpha adrenergic receptors. The mechanisms underlying the thermogenic response to alpha adrenergic receptors are enigmatic as are the mechanisms underlying adenosine modulation of this response and the elucidation of both are long term objectives of this research project. The thermogenic response to activation of alpha-1 adrenergic receptors is associated with the activation of both phospholipase C and phospholipase A2 causing the breakdown of phosphoinositides and other membrane phospholipids and the accumulation of inositol phosphates, diacylglcerol and arachidonic acid. The present research seeks a more detailed understanding of alpha adrenergic regulation of phospholipid metabolism in these cells by studying phospholipase C and A2 activities in plasma membranes isolated from brown adipocytes. Subsequent experiments will investigate the mechanisms by which adenosine antagonizes the cellular responses to alpha-1 receptor activation. These experiments will test the hypothesis that adenosine acts by uncoupling alpha-1 receptors from either phospholipase C or phospholipase A2, and acts as an inhibitor of phosphoinositide breakdown and/or production of arachidonic acid in these cells. These studies will provide insight into the biochemical regulation of thermogenesis and will contribute information on the bimodal regulation of phospholipid metabolism in a unique cell type not previously investigated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK036090-04
Application #
3234423
Study Section
Metabolism Study Section (MET)
Project Start
1985-08-01
Project End
1992-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Type
Schools of Osteopathy
DUNS #
City
Stratford
State
NJ
Country
United States
Zip Code
08084