المؤلفون: Sabra-Makke, Lina, Maritan, Micol, Planchais, Julien, Boutant, Marie, Pégorier, Jean-Paul, Even, Patrick C., Vasseur-Cognet, Mireille, Bossard, Pascale

المصدر: Proceedings of the National Academy of Sciences of the United States of America; 3/12/2013, Vol. 110 Issue 11, p4333-4338, 6p

مصطلحات موضوعية: HYPOTHALAMUS, HYPOGLYCEMIA, DYSAUTONOMIA, OVALBUMINS, TRANSCRIPTION factors

مستخلص: The nuclear receptor Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) is an important coordinator of glucose homeostasis through its function in different organs such as the endocrine pancreas, adipose tissue, skeletal muscle, and liver. Recently we have demonstrated that COUP-TFII expression in the hypothalamus is restricted to a subpopulation of neurons expressing the steroidogenic factor 1 transcription factor, known to play a crucial role in glucose homeostasis. To understand the functional significance of COUP-TFII expression in the steroidogenic factor 1 neurons, we generated hypothalamic ventromedial nucleus-specific COUP-TFII KO mice using the cyclization recombination/locus of X-overP1 technology. The heterozygous mutant mice display insulin hypersensitivity and a leaner phenotype associated with increased energy expenditure and similar food intake. These mutant mice also present a defective counterregulation to hypoglycemia with altered glucagon secretion. Moreover, the mutant mice are more likely to develop hypoglycemia-associated autonomic failure in response to recurrent hypoglycemic or glucopenic events. Therefore, COUP-TFII expression levels in the ventromedial nucleus are keys in the ability to resist the onset of hypoglycemia-associated autonomic failure. [ABSTRACT FROM AUTHOR]

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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]

: Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)