White adipose tissue (WAT) is a tissue specialized for the storage and mobilization of lipid energy. Chronic activation of WAT beta-adrenergic receptors by certain physiological and pharmacological conditions, however, transforms the tissue into one resembling brown fat, a thermogenic organ. Hallmarks of this tissue plasticity include transient inflammation followed by the appearance of multilocular adipocytes and massive mitochondria! biogenesis within these cells. Although the multilocular cells resemble brown adipocytes, histological and biochemical evidence indicates they are not newly-recruited brown fat cells, but rather represent a novel phenotype. These cells have greatly expanded capacity for lipid oxidation that appears to limit local inflammation induced by excessive fatty acid efflux. A significant fraction of the multilocular adipocytes appear to derive from mature fat cells through a novel proliferative pathway. These observations raise numerous fundamental questions regarding how the cellular plasticity takes place in WAT, and the function of the novel adipocyte phenotype. Multilocular adipocytes could represent a novel cellular target for anti-obesity and anti-diabetes therapeutics, and an understanding of the mechanisms controlling cellular plasticity in WAT could lead to novel points of therapeutic intervention for obesity and diabetes.
Our specific aims are: 1) To examine the functional and mechanistic relationships between adipocyte oxidative capacity and adipose tissue inflammation. 2) To determine the origin and fate of multilocular white adipocytes. 3) To examine mechanisms by which Adrb3 activation induces mitochondrial biogenesis in white adipocytes in vivo. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK062292-03A1
Application #
7140858
Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Haft, Carol R
Project Start
2002-07-01
Project End
2011-06-30
Budget Start
2006-07-20
Budget End
2007-06-30
Support Year
3
Fiscal Year
2006
Total Cost
$308,525
Indirect Cost
Name
Wayne State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
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