The storage and mobilization of lipids are fundamental cellular processes. In mammals, adipose tissue functions as a specialized lipid buffer that stores excess energy as triglyceride for systemic mobilization as free fatty acids (FFA). Nonetheless, virtually all cells have the ability to store and mobilize FFA;indeed, for some tissues FFA can provide the major source of metabolic energy. Excessive FFA can disrupt cellular function in a process that has been termed 'lipotoxicity," which is thought to be a major means by which obesity contributes to diabetes and cardiovascular disease. In theory, lipotoxicity can be brought about by excessive systemic supply of FFA from adipose tissue, or by an imbalance in FFA storage and mobilization in peripheral tissues. Thus, a mechanistic understanding of how cells assimilate, mobilize and channel FFA is an important biological question with broad implications for health and disease. Our long term goal is to provide a mechanistic understanding of cellular lipolysis so as to identify novel points of therapeutic intervention for the treatment of obesity and diabetes. We hypothesize that intracellular lipolysis is controlled by the orderly trafficking of specific proteins at the surface of specialized lipid droplets. This work will define the intracellular sites where lipolysis occurs, test specific models of dynamic protein-protein interactions, and determine the functional impact of those interactions in vitro and in vivo.

Public Health Relevance

The storage and mobilization of lipids are fundamental cellular processes that affect health and disease. This project investigates how cells breakdown stored fat. The long term goal is to identify novel points of therapeutic intervention for the treatment of obesity and diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK076629-05
Application #
8470630
Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Haft, Carol R
Project Start
2006-12-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$300,694
Indirect Cost
$102,869
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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Mottillo, Emilio P; Shen, Xiang Jun; Granneman, James G (2010) beta3-adrenergic receptor induction of adipocyte inflammation requires lipolytic activation of stress kinases p38 and JNK. Biochim Biophys Acta 1801:1048-55
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