Cardiovascular disease is, on average, the leading cause of death worldwide. Obesity is a related threat to human health which has reached epidemic proportions globally. The heparan sulfate proteoglycan (HSPG) syndecan-4 affects lipid metabolism at the intersection between both of these health concerns. Syndecan-4 is a ubiquitous molecule found at the surfaces of most animal cells. The high structural heterogeneity of HSPGs facilitates their interaction with a variety of molecules, including several involved in lipid metabolism. Additionally, syndecan-4 has been implicated in cell growth signaling and the differentiation and growth of fat cells. Further basic science research in the specific role of syndecan-4 in lipid metabolism is crucial in order to provide a framework for understanding the role it may play in atherogenesis and obesity, and in identifying molecular targets for treatment. I hypothesize that loss of syndecan-4 function should alter lipid metabolism and adipogenesis. I propose to investigate changes in plasma and tissue lipid levels and other markers of lipid metabolism in normal and syndecan-4 knockout mouse models with normal and high-fat diets. Levels of all other major cell-surface HSPGs will be measured in knockout mouse tissues to determine any cross-regulatory effects associated with the impairment of syndecan-4 function. Effects on adipogenesis will be studied in cultured differentiating preadipocytes with syndecan-4 mRNA """"""""knocked down"""""""" via RNA interference methods. Finally, proteomics analysis will be performed to determine binding partners of syndecan-4 during the preadipocyte-adipocyte transition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DK065363-04
Application #
7092650
Study Section
Special Emphasis Panel (ZRG1-MBC-1 (29))
Program Officer
Agodoa, Lawrence Y
Project Start
2003-08-18
Project End
2007-08-17
Budget Start
2006-08-18
Budget End
2007-08-17
Support Year
4
Fiscal Year
2006
Total Cost
$35,317
Indirect Cost
Name
Cornell University
Department
Nutrition
Type
Schools of Earth Sciences/Natur
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850