التفاصيل البيبلوغرافية
| العنوان: |
The Nutritional Induction of COUP-TFII Gene Expression in Ventromedial Hypothalamic Neurons Is Mediated by the Melanocortin Pathway. |
| المؤلفون: |
Sabra-Makke, Lina, Tourrel-Cuzin, Cécile, Denis, Raphaël G. P., Moldes, Marthe, Pégorier, Jean-Paul, Luquet, Serge, Vasseur-Cognet, Mireille, Bossard, Pascale |
| المصدر: |
PLoS ONE; 2010, Vol. 5 Issue 10, p1-15, 15p |
| مصطلحات موضوعية: |
GENE expression, NUCLEAR receptors (Biochemistry), TRANSCRIPTION factors, HOMEOSTASIS, IMMUNOFLUORESCENCE, NEURAL circuitry, ENERGY metabolism, BIOENERGETICS, HORMONE receptors, HYPOTHALAMUS |
| مستخلص: |
Background: The nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an important coordinator of glucose homeostasis. We report, for the first time, a unique differential regulation of its expression by the nutritional status in the mouse hypothalamus compared to peripheral tissues. Methodology/Principal Findings: Using hyperinsulinemic-euglycemic clamps and insulinopenic mice, we show that insulin upregulates its expression in the hypothalamus. Immunofluorescence studies demonstrate that COUP-TFII gene expression is restricted to a subpopulation of ventromedial hypothalamic neurons expressing the melanocortin receptor. In GT1-7 hypothalamic cells, the MC4-R agonist MTII leads to a dose dependant increase of COUP-TFII gene expression secondarily to a local increase in cAMP concentrations. Transfection experiments, using a COUP-TFII promoter containing a functional cAMP responsive element, suggest a direct transcriptional activation by cAMP. Finally, we show that the fed state or intracerebroventricular injections of MTII in mice induce an increased hypothalamic COUP-TFII expression associated with a decreased hepatic and pancreatic COUP-TFII expression. Conclusions/Significance: These observations strongly suggest that hypothalamic COUP-TFII gene expression could be a central integrator of insulin and melanocortin signaling pathway within the ventromedial hypothalamus. COUP-TFII could play a crucial role in brain integration of circulating signal of hunger and satiety involved in energy balance regulation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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