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.
| Kong, Dong; Vong, Linh; Parton, Laura E et al. (2010) Glucose stimulation of hypothalamic MCH neurons involves K(ATP) channels, is modulated by UCP2, and regulates peripheral glucose homeostasis. Cell Metab 12:545-52 |
| Krauss, Stefan; Zhang, Chen-Yu; Lowell, Bradford B (2002) A significant portion of mitochondrial proton leak in intact thymocytes depends on expression of UCP2. Proc Natl Acad Sci U S A 99:118-22 |
| Baffy, Gyorgy; Zhang, Chen-Yu; Glickman, Jonathan N et al. (2002) Obesity-related fatty liver is unchanged in mice deficient for mitochondrial uncoupling protein 2. Hepatology 35:753-61 |
| Zhang, C Y; Baffy, G; Perret, P et al. (2001) Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 105:745-55 |
