Epigenetic-Imprinting Changes Caused by Neonatal Fasting Stress Protect From Future Fasting Stress
| Autor: | D. M. Denbow, Y. Jiang, Cynthia J. Denbow, N. Meiri |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Endocrinology Diabetes and Metabolism Epigenesis Genetic Histones 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Endocrinology Stress Physiological Internal medicine Histone methylation medicine Animals Epigenetics Brain-derived neurotrophic factor Endocrine and Autonomic Systems business.industry Brain-Derived Neurotrophic Factor Fasting Methylation DNA Methylation 030104 developmental biology Hypothalamus Histone methyltransferase business Chickens Chromatin immunoprecipitation 030217 neurology & neurosurgery Homeostasis Paraventricular Hypothalamic Nucleus |
| Zdroj: | Journal of Neuroendocrinology. 28 |
| ISSN: | 0953-8194 |
| DOI: | 10.1111/jne.12333 |
| Popis: | Unfavourable nutritional conditions during the neonatal critical period can cause both acute metabolic disorders and severe metabolic syndromes in later life. These phenomena have been tightly related to the epigenetic modification controlling the balance between satiety and hunger in the hypothalamus. In the present study, we investigated epigenetic modification associated with both the fasting stress effects and the short-term resilience to fasting stress in the hypothalamic paraventricular nucleus (PVN) of chicks. Fasting for 24 h at 3 days of age (D) (i.e. D3) significantly increased global methylation at lysine 27 of histone 3 (H3K27) and its specific histone methyltransferase (HMT) expression level in the PVN. Because global methylation could not fully reveal the changes at specific genes, the regulation of the gene for brain-derived neurotrophic factor (Bdnf), which was recently also found to have an anorexigenic effect, was evaluated as a potential target. Chromatin immunoprecipitation assay analysis revealed that tri- (me3) and di-methylated (me2) H3K27 exhibited an instant (on D4 only) and latent increase (on both D11 and D41), respectively, at the putative promoter of Bdnf after 24 h of fasting on D3. This indicated that fasting could regulate energy-expenditure-related genes via modifying methylation at H3K27, which we suspected might be a protective mechanism for keeping the inner environment homeostatic. To test this hypothesis, a short-term repetitive fasting stress was applied to chickens, which were fasted for 24 h either on D10 only or on both D3 and D10. It was found that pre-existing fasting on D3 could induce a short-term fasting resilience, which rescued the reduction of Bdnf expression from future fasting on D10. We call this phenomenon the ‘molecular memory’, which was mainly conducted by HMTs and H3K27me2/me3 in the PVN. In conclusion, chicks respond to fasting with dynamic methylation at H3K27 in the PVN during the neonatal critical period. This allows the PVN to form a ‘molecular memory’, which keeps the individual inner environment homeostatic and resilient to future fasting over the short term. |
| Databáze: | OpenAIRE |
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