The storage and mobilization of lipid are fundamental cellular processes, and its dysregulation contributes to numerous diseases including diabetes, atherosclerosis and cardiomyopathy. The central hypothesis of this proposal is that regulated lipolysis involves the orderly trafficking of lipases and co-activators to specialized lipid droplet structures that are organized by specific lipid droplet scaffold proteins. Recent data indicates that protein perilipin A (Plin) is a lipid droplet scaffold protein that coordinates trafficking of lipolytic proteins in adipocytes. The proposed work seeks to build on these results and will characterize the exact temporal ordering of interactions among these lipolytic proteins during PKA stimulated lipolysis in adipocytes in vitro and in situ. Compared to fat cell lipolysis, very little is known about the organization of lipolysis in muscle;however, our preliminary data indicates that Mldp, a novel lipid droplet protein, organizes lipolysis in muscle for intracellular fatty acid oxidation. Using a panel of novel reagents and techniques, we propose to dissect lipolytic trafficking and lipolysis in model myocytes and in true muscle fibers. We anticipate that knowledge of the specific molecular interactions that control ectopic lipid clearance will allow us to devise screens for small molecules that promote this activity, with the long term goal of identifying lead compounds for treatment of obesity-related lipotoxicity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK076629-02
Application #
7849748
Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Haft, Carol R
Project Start
2009-06-01
Project End
2011-08-31
Budget Start
2010-06-01
Budget End
2011-08-31
Support Year
2
Fiscal Year
2010
Total Cost
$266,000
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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