دورية أكاديمية
Inducible neuronal inactivation of Sim1 in adult mice causes hyperphagic obesity.
| العنوان: | Inducible neuronal inactivation of Sim1 in adult mice causes hyperphagic obesity. |
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| المؤلفون: | Tolson KP; McDermott Center for Human Growth and Development (K.P.T., T.G., D.M., U.Y., J.K., A.R.Z.) and Department of Internal Medicine (A.R.Z.), The University of Texas Southwestern Medical Center, Dallas, Texas 75390-8591., Gemelli T, Meyer D, Yazdani U, Kozlitina J, Zinn AR |
| المصدر: | Endocrinology [Endocrinology] 2014 Jul; Vol. 155 (7), pp. 2436-44. Date of Electronic Publication: 2014 Apr 28. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375040 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-7170 (Electronic) Linking ISSN: 00137227 NLM ISO Abbreviation: Endocrinology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : New York : Oxford University Press Original Publication: Los Angeles, Calif. : Association for the Study of Internal Secretions, |
| مواضيع طبية MeSH: | Basic Helix-Loop-Helix Transcription Factors/*metabolism , Hyperphagia/*metabolism , Neurons/*metabolism , Obesity/*metabolism , Repressor Proteins/*metabolism, Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Body Weight/drug effects ; Bone Density Conservation Agents/pharmacology ; Eating/drug effects ; Energy Metabolism/drug effects ; Female ; Homeostasis/drug effects ; Male ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Neuropeptides/metabolism ; Oxytocin/metabolism ; Paraventricular Hypothalamic Nucleus/metabolism ; Repressor Proteins/genetics ; Tamoxifen/pharmacology |
| مستخلص: | Germline haploinsufficiency of human or mouse Sim1 is associated with hyperphagic obesity. Sim1 encodes a transcription factor required for proper formation of the paraventricular (PVN), supraoptic, and anterior periventricular hypothalamic nuclei. Sim1 expression persists in these neurons in adult mice, raising the question of whether it plays a physiologic role in regulation of energy balance. We previously showed that Sim1 heterozygous mice had normal numbers of PVN neurons that were hyporesponsive to melanocortin 4 receptor agonism and showed reduced oxytocin expression. Furthermore, conditional postnatal neuronal inactivation of Sim1 also caused hyperphagic obesity and decreased hypothalamic oxytocin expression. PVN projections to the hindbrain, where oxytocin is thought to act to modulate satiety, were anatomically intact in both Sim1 heterozygous and conditional knockout mice. These experiments provided evidence that Sim1 functions in energy balance apart from its role in hypothalamic development but did not rule out effects of Sim1 deficiency on postnatal hypothalamic maturation. To address this possibility, we used a tamoxifen-inducible, neural-specific Cre transgene to conditionally inactivate Sim1 in adult mice with mature hypothalamic circuitry. Induced Sim1 inactivation caused increased food and water intake and decreased expression of PVN neuropeptides, especially oxytocin and vasopressin, with no change in energy expenditure. Sim1 expression was not required for survival of PVN neurons. The results corroborate previous evidence that Sim1 acts physiologically as well as developmentally to regulate body weight. Inducible knockout mice provide a system for studying Sim1's physiologic function in energy balance and identifying its relevant transcriptional targets in the hypothalamus. |
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| معلومات مُعتمدة: | RL1 DK081185 United States DK NIDDK NIH HHS; R01 DK079986 United States DK NIDDK NIH HHS; R01DK079986 United States DK NIDDK NIH HHS; RL1DK081185 United States DK NIDDK NIH HHS; UL1 DE019584 United States DE NIDCR NIH HHS; UL1DE019584 United States DE NIDCR NIH HHS |
| المشرفين على المادة: | 0 (Basic Helix-Loop-Helix Transcription Factors) 0 (Bone Density Conservation Agents) 0 (Neuropeptides) 0 (Repressor Proteins) 0 (Sim1 protein, mouse) 094ZI81Y45 (Tamoxifen) 50-56-6 (Oxytocin) |
| تواريخ الأحداث: | Date Created: 20140430 Date Completed: 20140825 Latest Revision: 20211021 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC4060186 |
| DOI: | 10.1210/en.2013-2125 |
| PMID: | 24773343 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-7170 |
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| DOI: | 10.1210/en.2013-2125 |