Identification of Novel Mechanisms in the Hypothalamus Linked to Adiposity.
Byerly, Mardi Susanna
Porter, Tom E
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Body composition is a trait regulated by many different genes, giving rise to the severity of the phenotype in a continuous manner. We propose to investigate genetic interactions regulating obesity by focusing on genetic heretibility and genes that interact with Brain-Derived Neurotrophic Factor (BDNF) or thyroid hormone. We have utilized a novel model of obesity, genetically selected chicken lines, because differences in abdominal fat between the lines are based on genotype alone, independent of environmental influences. In order to identify novel gene networks that might give rise to the obese phenotype, hypothalamic gene expression was characterized using microarray technology. Hypothalamic neuronal cell cultures and in vivo manipulations were performed to verify that BDNF interacts with the hypothalamic-pituitary-thyroid axis, while simultaneously identifying novel genes that may interact together or independently of BDNF. A hypothetical model suggesting how BDNF and thyroid hormone reciprocally modulate genes in the hypothalamus already known to contribute to energy regulation was developed.