Abstract

Recently a protein was cloned that has high homology with UCP-1 and was identified, UCP-2. Given this high homology with UCP-1 and its wide tissue distribution including the muscle, the applicant's goal is to ascertain the functional significance of the protein. He hypothesizes that UCP-2 is a mitochondrial uncoupling protein, and that it plays a significant role in thermogenesis and overall energy balance. To address this hypothesis the applicant proposes to: (1) determine the tissue, cellular and subcellular localization of UCP-2, and to assess the regulation of its expression by metabolic states, cytokines, and hormones; (2) determine the consequences of UCP-2 expression on mitochondrial and cellular respiration and to identify intracellular signals which regulate UCP-2 activity; (3) identify cis-regulatory elements and trans.-acting factors which are importent in controlling UCP-2 gene expression; and (4) determine in vivo the physiologic consequences of altered UCP-2 gene expression on systemic energy balance using transgenic mice and knock-our mice. In a followup letter, Dr. Lowell reports that his group (and others) have cloned another UCP, UCP-3. He now plans to focus most attention on UCP-3 rather than UCP-2, though in some experiments both can be studied.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK053477-02
Application #
2856834
Study Section
Nutrition Study Section (NTN)
Program Officer
Yanovski, Susan Z
Project Start
1998-01-15
Project End
2001-12-31
Budget Start
1999-02-01
Budget End
1999-12-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215