Hypothalamic mTORC1 Signaling Controls Sympathetic Nerve Activity and Arterial Pressure and Mediates Leptin Effects
| Autor: | Caroline Fernandes-Santos, Deng-Fu Guo, Kamal Rahmouni, Shannon M. Harlan, Donald A. Morgan |
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| Rok vydání: | 2013 |
| Předmět: |
Leptin
medicine.medical_specialty Sympathetic nervous system Sympathetic Nervous System Class I Phosphatidylinositol 3-Kinases Physiology Hypothalamus mTORC1 Mechanistic Target of Rapamycin Complex 1 030204 cardiovascular system & hematology Biology Article Rats Sprague-Dawley Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Leucine Internal medicine medicine Animals Arterial Pressure Phosphorylation RNA Small Interfering Molecular Biology PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors 030304 developmental biology Sirolimus 0303 health sciences Leptin receptor TOR Serine-Threonine Kinases Proteins Ribosomal Protein S6 Kinases 70-kDa Rostral ventrolateral medulla Cell Biology Rats 3. Good health Mice Inbred C57BL medicine.anatomical_structure Endocrinology Multiprotein Complexes Receptors Leptin RNA Interference biological phenomena cell phenomena and immunity Signal transduction Signal Transduction |
| Zdroj: | Cell Metabolism. 17(4):599-606 |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2013.02.017 |
| Popis: | SummaryThe fundamental importance of the hypothalamus in the regulation of autonomic and cardiovascular functions is well established. However, the molecular processes involved are not well understood. Here, we show that the mammalian (or mechanistic) target of rapamycin (mTOR) signaling in the hypothalamus is tied to the activity of the sympathetic nervous system and to cardiovascular function. Modulation of mTOR complex 1 (mTORC1) signaling caused dramatic changes in sympathetic traffic, blood flow, and arterial pressure. Our data also demonstrate the importance of hypothalamic mTORC1 signaling in transducing the sympathetic and cardiovascular actions of leptin. Moreover, we show that the PI3K pathway links the leptin receptor to mTORC1 signaling and that changes in its activity impact sympathetic traffic and arterial pressure. These findings establish mTORC1 activity in the hypothalamus as a key determinant of sympathetic and cardiovascular regulation and suggest that dysregulated hypothalamic mTORC1 activity may influence the development of cardiovascular diseases. |
| Databáze: | OpenAIRE |
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