Abstract

The agouti peptide plays a central role in determining the type of melanin (eumelanins or phaeomelanins) produced within the melanocyte. The normal action of agouti is most likely as an antagonist of the MSH receptor, MC1-R. In the mouse, ectopic expression of agouti leads to obesity, potentially mediated through an interaction with (hypothalamic) MC4-R.
The aims of the proposed project are: 1) To study the structure the agouti peptide to define the specificity of its effects on pigmentation and obesity; 2) to determine the binding site and mechanism of antagonism of melanocortin receptors; 3) to test the hypothesis that agouti may act independent of melanocortin receptor antagonism; 4) to identify other members of the agouti family that may be more relevant to endogenous antagonism of MC4-R; and, 5) to test the hypothesis that antagonism of MC4-R is responsible for agouti-mediated obesity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK051730-03
Application #
2770599
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Smith, Philip F
Project Start
1996-09-30
Project End
2000-08-31
Budget Start
1998-09-25
Budget End
1999-08-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Oregon Health and Science University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239

  Publications

Gruber, Kenneth A; Fan, Wei; Akerberg, Helena et al. (2009) Neuropeptide Y and gamma-melanocyte stimulating hormone (gamma-MSH) share a common pressor mechanism of action. Endocrine 35:312-24
Ni, Xi-Ping; Butler, Andrew A; Cone, Roger D et al. (2006) Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones. J Hypertens 24:2239-46
Morgan, Caurnel; Cone, Roger D (2006) Melanocortin-5 receptor deficiency in mice blocks a novel pathway influencing pheromone-induced aggression. Behav Genet 36:291-300
Takahashi, Kanji A; Cone, Roger D (2005) Fasting induces a large, leptin-dependent increase in the intrinsic action potential frequency of orexigenic arcuate nucleus neuropeptide Y/Agouti-related protein neurons. Endocrinology 146:1043-7
Morgan, Caurnel; Thomas, Ruth E; Cone, Roger D (2004) Melanocortin-5 receptor deficiency promotes defensive behavior in male mice. Horm Behav 45:58-63
Morgan, Caurnel; Thomas, Ruth E; Ma, Weidong et al. (2004) Melanocortin-5 receptor deficiency reduces a pheromonal signal for aggression in male mice. Chem Senses 29:111-5
Marks, Daniel L; Boucher, Nathalie; Lanouette, Christian-Marc et al. (2004) Ala67Thr polymorphism in the Agouti-related peptide gene is associated with inherited leanness in humans. Am J Med Genet A 126A:267-71
Fekete, Csaba; Marks, Daniel L; Sarkar, Sumit et al. (2004) Effect of Agouti-related protein in regulation of the hypothalamic-pituitary-thyroid axis in the melanocortin 4 receptor knockout mouse. Endocrinology 145:4816-21
Horvath, Tamas L; Diano, Sabrina; Tschop, Matthias (2004) Brain circuits regulating energy homeostasis. Neuroscientist 10:235-46
Cowley, Michael A; Smith, Roy G; Diano, Sabrina et al. (2003) The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37:649-61

Showing the most recent 10 out of 22 publications