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Activators of Adipocyte Fatty Acid Oxidation

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
66359
Program Year/Program:
2003 / SBIR
Agency Tracking Number:
DK065430
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
ADIPOGENIX, INC.
ADIPOGENIX, INC. 801 ALBANY ST, S112 BOSTON, MA 02119 0251
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2003
Title: Activators of Adipocyte Fatty Acid Oxidation
Agency: HHS
Contract: 1R43DK065430-01
Award Amount: $99,944.00
 

Abstract:

DESCRIPTION (provided by applicant): Obesity is a well-established risk factor for a number of diseases, including type 2 diabetes and coronary heart disease. Existing drug and dietary treatments for obesity are only modestly effective. An approach that is very likely to be effective in treating obesity and with a good side effect profile is a drug that acts directly on lipid metabolism in the fat cell. The mission of AdipoGenix, Inc. is to discover and develop novel therapeutics acting at the level of the fat cell for treating obesity, diabetes, and related metabolic disorders. The enzyme carnitine palmitoyltransferase I (CPT I) is the critical control point for fatty acid metabolism in the cell and provides the main switch between free fatty acid (FFA) oxidation to CO2 and esterification to triglyceride (TG). A slight change in the balance between oxidation and synthesis could have a major impact on fat stores. Malonyl-CoA, an allosteric inhibitor of CPT I, regulates FFA oxidation and, consequently, fat storage. Compounds that interfere with the effect of malonyl-CoA on CPT I can promote CPT I activity and, thereby, FFA oxidation. We propose to characterize the differentiation- and fat depot-dependent expression of CPT I isoforms in human preadipocytes, and to develop high-throughput screens to identify compounds that relieve the inhibitory effect of malonyl-CoA on CPT I and thereby stimulate oxidation. Relative quantitative RTPCR and Western blotting will be used to analyze expression of CPT I isoforms in human adipocytes during differentiation and from different anatomical depots. A high-throughput assay to measure activity of CPT I in isolated mitochondrial preparations and in permeabilized human adipocytes in the presence and absence of the inhibitor malonyl-CoA will be developed. In parallel, a high-throughput assay to measure oxygen consumption in human adipocytes using an oxygen-sensing microplate-based system will be developed. The assay determined to be most suitable for HTS will be used to screen chemical libraries in Phase II. Achievement of these aims will establish a viable HTS assay and secondary assays for identifying compounds that activate CPT I and increase oxidation in human adipocytes. Development of such compounds may lead to therapeutic interventions that are effective for modulating lipid metabolism and treating obesity.

Principal Investigator:

Cydney C. Brooks
6176385351
BROOKS@BU.EDU

Business Contact:

Gerri Waloga
6176386389
GWALOGA@BU.EDU
Small Business Information at Submission:

ADIPOGENIX, INC.
ADIPOGENIX, INC. 801 ALBANY ST, S112 BOSTON, MA 02119

EIN/Tax ID: 043382537
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No