Submitted on October 5, 2008
Revised on January 12, 2009
Accepted on January 14, 2009
Effects of BDNF, T3 and Corticosterone on expression of the hypothalamic obesity gene network in vivo and in vitro
Mardi S Byerly1, Jean Simon2, Elisabeth Lebihan-Duval3, Michel J. Duclos3, Larry A. Cogburn4, and Tom E. Porter1*
1 University of Maryland
2 INRA-SRA
3 Centre de Recherches de Tours
4 University of Delaware
* To whom correspondence should be addressed. E-mail: teporter{at}umd.edu.
Hypothalamic neuropeptides, neurotrophins and systemic hormones modulate food intake and body composition. Although advances toward elucidating these interactions have been made, many aspects of the underlying mechanisms remain vague. Hypothalami from Fat and Lean chicken lines were assessed for differential expression of anabolic/orexigenic and catabolic/anorexigenic genes. Effects of triiodothyronine (T3), corticosterone (Cort) and Brain-Derived Neurotrophic Factor (BDNF) on expression of anabolic/orexigenic and catabolic/anorexigenic genes was tested in cultures of hypothalamic neurons. From this, we found that BDNF increased and T3 decreased gene expression for BDNF, leptin receptor (LEPR), pro-opiomelanocortin (POMC), thyrotropin releasing hormone (TRH) and agouti related protein (AGRP). Thyroid hormone levels were manipulated during development to show that T3 inhibited BDNF, TRH and BDNF receptor (TrkB) gene expression. Delivery of T3, Cort, T3 plus Cort, or vehicle in vivo continuously for 72 hours indicated that Cort and T3 have overlapping roles in regulating TRH, LEPR, and POMC gene expression, and that Cort and T3 regulate BDNF, Neuropeptide Y and AGRP in opposite directions. Collectively, these findings suggest that interactions between the neuropeptide, BDNF, the hormones T3 and/or Cort may constitute a homeostatic mechanism that links hypothalamic energy regulation controlling body composition.
