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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Publicado:	2001
Materias:	Electrophysiology Hormones Metabolism Proteins Neurons Neural networks 4 aminobutyric acid cation channel green fluorescent protein leptin neuropeptide Y proopiomelanocortin action potential animal cell animal experiment arcuate nucleus article controlled study depolarization embryo gene expression gene targeting male mouse nerve cell nerve cell network nonhuman priority journal regulatory mechanism transgenic mouse Action Potentials Animals Animals, Genetically Modified Anorexia Arcuate Nucleus Evoked Potentials gamma-Aminobutyric Acid Green Fluorescent Proteins Leptin Luminescent Proteins Male Mice Mice, Inbred C57BL Nerve Net Neural Inhibition Neuropeptide Y Pro-Opiomelanocortin Animalia Mus musculus
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00280836_v411_n6836_p480_Cowley http://hdl.handle.net/20.500.12110/paper_00280836_v411_n6836_p480_Cowley
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00280836_v411_n6836_p480_Cowley
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spelling	paper:paper_00280836_v411_n6836_p480_Cowley2023-06-08T14:54:42Z Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus Electrophysiology Hormones Metabolism Proteins Neurons Neural networks 4 aminobutyric acid cation channel green fluorescent protein leptin neuropeptide Y proopiomelanocortin action potential animal cell animal experiment arcuate nucleus article controlled study depolarization embryo gene expression gene targeting male mouse nerve cell nerve cell network nonhuman priority journal regulatory mechanism transgenic mouse Action Potentials Animals Animals, Genetically Modified Anorexia Arcuate Nucleus Electrophysiology Evoked Potentials gamma-Aminobutyric Acid Green Fluorescent Proteins Leptin Luminescent Proteins Male Mice Mice, Inbred C57BL Nerve Net Neural Inhibition Neurons Neuropeptide Y Pro-Opiomelanocortin Animalia Mus musculus 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. 2001 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00280836_v411_n6836_p480_Cowley http://hdl.handle.net/20.500.12110/paper_00280836_v411_n6836_p480_Cowley
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Electrophysiology Hormones Metabolism Proteins Neurons Neural networks 4 aminobutyric acid cation channel green fluorescent protein leptin neuropeptide Y proopiomelanocortin action potential animal cell animal experiment arcuate nucleus article controlled study depolarization embryo gene expression gene targeting male mouse nerve cell nerve cell network nonhuman priority journal regulatory mechanism transgenic mouse Action Potentials Animals Animals, Genetically Modified Anorexia Arcuate Nucleus Electrophysiology Evoked Potentials gamma-Aminobutyric Acid Green Fluorescent Proteins Leptin Luminescent Proteins Male Mice Mice, Inbred C57BL Nerve Net Neural Inhibition Neurons Neuropeptide Y Pro-Opiomelanocortin Animalia Mus musculus
spellingShingle	Electrophysiology Hormones Metabolism Proteins Neurons Neural networks 4 aminobutyric acid cation channel green fluorescent protein leptin neuropeptide Y proopiomelanocortin action potential animal cell animal experiment arcuate nucleus article controlled study depolarization embryo gene expression gene targeting male mouse nerve cell nerve cell network nonhuman priority journal regulatory mechanism transgenic mouse Action Potentials Animals Animals, Genetically Modified Anorexia Arcuate Nucleus Electrophysiology Evoked Potentials gamma-Aminobutyric Acid Green Fluorescent Proteins Leptin Luminescent Proteins Male Mice Mice, Inbred C57BL Nerve Net Neural Inhibition Neurons Neuropeptide Y Pro-Opiomelanocortin Animalia Mus musculus Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
topic_facet	Electrophysiology Hormones Metabolism Proteins Neurons Neural networks 4 aminobutyric acid cation channel green fluorescent protein leptin neuropeptide Y proopiomelanocortin action potential animal cell animal experiment arcuate nucleus article controlled study depolarization embryo gene expression gene targeting male mouse nerve cell nerve cell network nonhuman priority journal regulatory mechanism transgenic mouse Action Potentials Animals Animals, Genetically Modified Anorexia Arcuate Nucleus Electrophysiology Evoked Potentials gamma-Aminobutyric Acid Green Fluorescent Proteins Leptin Luminescent Proteins Male Mice Mice, Inbred C57BL Nerve Net Neural Inhibition Neurons Neuropeptide Y Pro-Opiomelanocortin Animalia Mus musculus
description	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.
title	Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
title_short	Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
title_full	Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
title_fullStr	Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
title_full_unstemmed	Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
title_sort	leptin activates anorexigenic pomc neurons through a neural network in the arcuate nucleus
publishDate	2001
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00280836_v411_n6836_p480_Cowley http://hdl.handle.net/20.500.12110/paper_00280836_v411_n6836_p480_Cowley
_version_	1768544398261354496

Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus

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