title: Dendritically targeted Bdnf mRNA is essential for energy balance and response to leptin.
abstract: Mutations in the Bdnf gene, which produces transcripts with either short or long 3' untranslated regions (3' UTRs), cause human obesity; however, the precise role of brain-derived neurotrophic factor (BDNF) in the regulation of energy balance is unknown. Here we show the relationship between Bdnf mRNA with a long 3' UTR (long 3' UTR Bdnf mRNA), leptin, neuronal activation and body weight. We found that long 3' UTR Bdnf mRNA was enriched in the dendrites of hypothalamic neurons and that insulin and leptin could stimulate its translation in dendrites. Furthermore, mice harboring a truncated long Bdnf 3' UTR developed severe hyperphagic obesity, which was completely reversed by viral expression of long 3' UTR Bdnf mRNA in the hypothalamus. In these mice, the ability of leptin to activate hypothalamic neurons and inhibit food intake was compromised despite normal activation of leptin receptors. These results reveal a novel mechanism linking leptin action to BDNF expression during hypothalamic-mediated regulation of body weight, while also implicating dendritic protein synthesis in this process.
authors.affiliation: Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Guey-Ying
authors.initials: GY
authors.lastname: Liao
authors.forename: Juan Ji
authors.initials: JJ
authors.lastname: An
authors.forename: Kusumika
authors.initials: K
authors.lastname: Gharami
authors.forename: Emily G
authors.initials: EG
authors.lastname: Waterhouse
authors.forename: Filip
authors.initials: F
authors.lastname: Vanevski
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Jones
authors.forename: Baoji
authors.initials: B
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects* / Q000235:genetics; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000166:cytology; D007328:Insulin / Q000494:pharmacology; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D020413:3' Untranslated Regions; D019208:Brain-Derived Neurotrophic Factor; D007328:Insulin; D020738:Leptin; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D011972:Receptor, Insulin; D020813:Receptor, trkB