Effects of BDNF, T3, and corticosterone on expression of the hypothalamic obesity gene network in vivo and in vitro.
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 (T(3)), corticosterone (Cort), and brain-derived neurotrophic factor (BDNF) on expression of anabolic/orexigenic and catabolic/anorexigenic genes were tested in cultures of hypothalamic neurons. From this, we found that BDNF increased and T(3) 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 T(3) inhibited BDNF, TRH, and BDNF receptor gene expression. Delivery of T(3), Cort, T(3) plus Cort, or vehicle in vivo continuously for 72 h indicated that Cort and T(3) have overlapping roles in regulating TRH, LEPR, and POMC gene expression and that Cort and T(3) regulate BDNF, neuropeptide Y, and AGRP in opposite directions. Collectively, these findings suggest that interactions between the neuropeptide BDNF and the hormones T(3) and/or Cort may constitute a homeostatic mechanism that links hypothalamic energy regulation controlling body composition.
Byerly
Mardi S
MS
Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20712, USA.
Simon
Jean
J
Lebihan-Duval
Elisabeth
E
Duclos
Michel J
MJ
Cogburn
Larry A
LA
Porter
Tom E
TE
D000367:Age Factors; D000818:Animals; D001823:Body Composition / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D003345:Corticosterone / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D007031:Hypothalamus / Q000196:embryology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary; D012333:RNA, Messenger / Q000378:metabolism; D020218:Response Elements; D014284:Triiodothyronine / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D014284:Triiodothyronine; D003345:Corticosterone