Dendritically targeted Bdnf mRNA is essential for energy balance and response to leptin
| Autor: | Emily G. Waterhouse, Filip Vanevski, Guey-Ying Liao, Juan Ji An, Kevin R. Jones, Baoji Xu, Kusumika Gharami |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Leptin
Male Untranslated region Mice 0302 clinical medicine Transduction Genetic Neurotrophic factors Insulin 3' Untranslated Regions Cells Cultured Neurons Regulation of gene expression 0303 health sciences digestive oral and skin physiology Age Factors General Medicine Female Microtubule-Associated Proteins Proto-Oncogene Proteins c-fos Signal Transduction medicine.medical_specialty Green Fluorescent Proteins Hypothalamus Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Internal medicine medicine Animals Humans Receptor trkB Obesity RNA Messenger 030304 developmental biology Brain-derived neurotrophic factor Analysis of Variance Messenger RNA Leptin receptor Three prime untranslated region Brain-Derived Neurotrophic Factor Body Weight Dendrites Receptor Insulin Mice Inbred C57BL Disease Models Animal Endocrinology Gene Expression Regulation nervous system Energy Metabolism 030217 neurology & neurosurgery |
| Zdroj: | Nature medicine |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm.2687 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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