Obesity and hyperphagia are phenotypes of conditional mutants lacking Brain-Derived Neurotrophic Factor (BDNF) in the brain after birth. Further investigation has also implicated the BDNF gene in both human obesity and anorexia. Since obesity is a trait regulated by many different genes, with allelic segregation of these genes giving rise to the severity of the phenotype in a continuous manner, we propose to investigate genetic interactions regulating obesity by focusing on genes that interact with BDNF. It should be noted, that this model of obesity is novel because it gives rise to an obese phenotype based on genotype alone, independent of the need for environmental influences. We are proposing that BDNF may interact with the hypothalamic-pituitary thyroid (HPT) axis to modulate hypothalamic energy regulation and food intake. We plan to utilize [microarrays] neuronal cell culture and in vivo manipulations to verify the interactions of BDNF with the HPT axis, while simultaneously identifying [novel] genes that may interact together or independently of BDNF expression to induce the obese phenotype observed in our quantitative trait animal model.

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 #
5F31DK074380-02
Application #
7256282
Study Section
Special Emphasis Panel (ZRG1-DIG-H (29))
Program Officer
Agodoa, Lawrence Y
Project Start
2006-07-01
Project End
2007-12-31
Budget Start
2007-07-01
Budget End
2007-12-31
Support Year
2
Fiscal Year
2007
Total Cost
$16,229
Indirect Cost
Name
University of Maryland College Park
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
790934285
City
College Park
State
MD
Country
United States
Zip Code
20742
Byerly, Mardi S; Simon, Jean; Cogburn, Larry A et al. (2010) Transcriptional profiling of hypothalamus during development of adiposity in genetically selected fat and lean chickens. Physiol Genomics 42:157-67
Byerly, Mardi S; Simon, Jean; Lebihan-Duval, Elisabeth et al. (2009) Effects of BDNF, T3, and corticosterone on expression of the hypothalamic obesity gene network in vivo and in vitro. Am J Physiol Regul Integr Comp Physiol 296:R1180-9