Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
The administration of leptin to leptin-deficient humans, and the analogous Lepob/Lepob mice, effectively reduces hyperphagia and obesity. But common obesity is associated with elevated leptin, which suggests that obese humans are resistant to this adipocyte hormone. In addition to regulating long-te...
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| Otros Autores: | , , , , , , |
| Formato: | Capítulo de libro |
| Lenguaje: | Inglés |
| Publicado: |
2001
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| Acceso en línea: | Registro en Scopus DOI Handle Registro en la Biblioteca Digital |
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| LEADER | 11228caa a22014057a 4500 | ||
|---|---|---|---|
| 001 | PAPER-20640 | ||
| 003 | AR-BaUEN | ||
| 005 | 20230518205203.0 | ||
| 008 | 190411s2001 xx ||||fo|||| 00| 0 eng|d | ||
| 024 | 7 | |2 scopus |a 2-s2.0-0035942777 | |
| 024 | 7 | |2 cas |a gamma-Aminobutyric Acid, 56-12-2; Green Fluorescent Proteins, 147336-22-9; Leptin; Luminescent Proteins; Neuropeptide Y; Pro-Opiomelanocortin, 66796-54-1 | |
| 040 | |a Scopus |b spa |c AR-BaUEN |d AR-BaUEN | ||
| 030 | |a NATUA | ||
| 100 | 1 | |a Cowley, M.A. | |
| 245 | 1 | 0 | |a Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus |
| 260 | |c 2001 | ||
| 270 | 1 | 0 | |m Cone, R.D.; Vollum Institute, Oregon Health Sciences University, Portland, OR 97201-3098, United States; email: cone@ohsu.edu |
| 506 | |2 openaire |e Política editorial | ||
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| 520 | 3 | |a The administration of leptin to leptin-deficient humans, and the analogous Lepob/Lepob mice, effectively reduces hyperphagia and obesity. But common obesity is associated with elevated leptin, which suggests that obese humans are resistant to this adipocyte hormone. In addition to regulating long-term energy balance, leptin also rapidly affects neuronal activity. Proopiomelanocortin (POMC) and neuropeptide-Y types of neurons in the arcuate nucleus of the hypothalamus are both principal sites of leptin receptor expression and the source of potent neuropeptide modulators, melanocortins and neuropeptide Y, which exert opposing effects on feeding and metabolism. These neurons are therefore ideal for characterizing leptin action and the mechanism of leptin resistance; however, their diffuse distribution makes them difficult to study. Here we report electrophysiological recordings on POMC neurons, which we identified by targeted expression of green fluorescent protein in transgenic mice. Leptin increases the frequency of action potentials in the anorexigenic POMC neurons by two mechanisms: depolarization through a nonspecific cation channel; and reduced inhibition by local orexigenic neuropeptide-Y/GABA (γ-aminobutyric acid) neurons. Furthermore, we show that melanocortin peptides have an autoinhibitory effect on this circuit. On the basis of our results, we propose an integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamus. |l eng | |
| 593 | |a Vollum Institute, Oregon Health Sciences University, Portland, OR 97201-3098, United States | ||
| 593 | |a Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Department of Biology, University of Buenos Aires, 1428, Argentina | ||
| 593 | |a Reproductive Neurosciences Unit, Department of Obstetrics and Gynecology, Yale Medical School, New Haven, CT 06520, United States | ||
| 593 | |a Department of Neurobiology, Yale Medical School, New Haven, CT 06520, United States | ||
| 690 | 1 | 0 | |a ELECTROPHYSIOLOGY |
| 690 | 1 | 0 | |a HORMONES |
| 690 | 1 | 0 | |a METABOLISM |
| 690 | 1 | 0 | |a PROTEINS |
| 690 | 1 | 0 | |a NEURONS |
| 690 | 1 | 0 | |a NEURAL NETWORKS |
| 690 | 1 | 0 | |a 4 AMINOBUTYRIC ACID |
| 690 | 1 | 0 | |a CATION CHANNEL |
| 690 | 1 | 0 | |a GREEN FLUORESCENT PROTEIN |
| 690 | 1 | 0 | |a LEPTIN |
| 690 | 1 | 0 | |a NEUROPEPTIDE Y |
| 690 | 1 | 0 | |a PROOPIOMELANOCORTIN |
| 690 | 1 | 0 | |a ACTION POTENTIAL |
| 690 | 1 | 0 | |a ANIMAL CELL |
| 690 | 1 | 0 | |a ANIMAL EXPERIMENT |
| 690 | 1 | 0 | |a ARCUATE NUCLEUS |
| 690 | 1 | 0 | |a ARTICLE |
| 690 | 1 | 0 | |a CONTROLLED STUDY |
| 690 | 1 | 0 | |a DEPOLARIZATION |
| 690 | 1 | 0 | |a EMBRYO |
| 690 | 1 | 0 | |a GENE EXPRESSION |
| 690 | 1 | 0 | |a GENE TARGETING |
| 690 | 1 | 0 | |a MALE |
| 690 | 1 | 0 | |a MOUSE |
| 690 | 1 | 0 | |a NERVE CELL |
| 690 | 1 | 0 | |a NERVE CELL NETWORK |
| 690 | 1 | 0 | |a NONHUMAN |
| 690 | 1 | 0 | |a PRIORITY JOURNAL |
| 690 | 1 | 0 | |a REGULATORY MECHANISM |
| 690 | 1 | 0 | |a TRANSGENIC MOUSE |
| 690 | 1 | 0 | |a ACTION POTENTIALS |
| 690 | 1 | 0 | |a ANIMALS |
| 690 | 1 | 0 | |a ANIMALS, GENETICALLY MODIFIED |
| 690 | 1 | 0 | |a ANOREXIA |
| 690 | 1 | 0 | |a ARCUATE NUCLEUS |
| 690 | 1 | 0 | |a ELECTROPHYSIOLOGY |
| 690 | 1 | 0 | |a EVOKED POTENTIALS |
| 690 | 1 | 0 | |a GAMMA-AMINOBUTYRIC ACID |
| 690 | 1 | 0 | |a GREEN FLUORESCENT PROTEINS |
| 690 | 1 | 0 | |a LEPTIN |
| 690 | 1 | 0 | |a LUMINESCENT PROTEINS |
| 690 | 1 | 0 | |a MALE |
| 690 | 1 | 0 | |a MICE |
| 690 | 1 | 0 | |a MICE, INBRED C57BL |
| 690 | 1 | 0 | |a NERVE NET |
| 690 | 1 | 0 | |a NEURAL INHIBITION |
| 690 | 1 | 0 | |a NEURONS |
| 690 | 1 | 0 | |a NEUROPEPTIDE Y |
| 690 | 1 | 0 | |a PRO-OPIOMELANOCORTIN |
| 690 | 1 | 0 | |a ANIMALIA |
| 690 | 1 | 0 | |a MUS MUSCULUS |
| 700 | 1 | |a Smart, J.L. | |
| 700 | 1 | |a Rubinstein, M. | |
| 700 | 1 | |a Cerdán, M.G. | |
| 700 | 1 | |a Diano, S. | |
| 700 | 1 | |a Horvath, T.L. | |
| 700 | 1 | |a Cone, R.D. | |
| 700 | 1 | |a Low, M.J. | |
| 773 | 0 | |d 2001 |g v. 411 |h pp. 480-484 |k n. 6836 |p Nature |x 00280836 |w (AR-BaUEN)CENRE-48 |t Nature | |
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| 856 | 4 | 0 | |u https://doi.org/10.1038/35078085 |y DOI |
| 856 | 4 | 0 | |u https://hdl.handle.net/20.500.12110/paper_00280836_v411_n6836_p480_Cowley |y Handle |
| 856 | 4 | 0 | |u https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00280836_v411_n6836_p480_Cowley |y Registro en la Biblioteca Digital |
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