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Mol Metab. 2018 Dec;18:120-133. doi: 10.1016/j.molmet.2018.08.007. Epub 2018 Sep 18.

Endocannabinoid and nitric oxide systems of the hypothalamic paraventricular nucleus mediate effects of NPY on energy expenditure.

Author information

1
Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, H-1083 Hungary.
2
Unite de Biologie Fonctionnelle et Adaptative, Centre National la Recherche Scientifique, Unité Mixte de Recherche 8251, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France.
3
Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, H-1083 Hungary; Multidisciplinary Doctoral School of Sciences and Technology, Budapest, H-1083 Hungary.
4
Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
5
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, MA, USA; Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA.
6
Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, H-1083 Hungary; Department of Neuroscience, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, H-1083 Hungary.
7
Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, H-1083 Hungary; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, MA, USA. Electronic address: fekete.csaba@koki.mta.hu.

Abstract

OBJECTIVE:

Neuropeptide Y (NPY) is one of the most potent orexigenic peptides. The hypothalamic paraventricular nucleus (PVN) is a major locus where NPY exerts its effects on energy homeostasis. We investigated how NPY exerts its effect within the PVN.

METHODS:

Patch clamp electrophysiology and Ca2+ imaging were used to understand the involvement of Ca2+ signaling and retrograde transmitter systems in the mediation of NPY induced effects in the PVN. Immuno-electron microscopy were performed to elucidate the subcellular localization of the elements of nitric oxide (NO) system in the parvocellular PVN. In vivo metabolic profiling was performed to understand the role of the endocannabinoid and NO systems of the PVN in the mediation of NPY induced changes of energy homeostasis.

RESULTS:

We demonstrated that NPY inhibits synaptic inputs of parvocellular neurons in the PVN by activating endocannabinoid and NO retrograde transmitter systems via mobilization of Ca2+ from the endoplasmic reticulum, suggesting that NPY gates the synaptic inputs of parvocellular neurons in the PVN to prevent the influence of non-feeding-related inputs. While intraPVN administered NPY regulates food intake and locomotor activity via NO signaling, the endocannabinoid system of the PVN selectively mediates NPY-induced decrease in energy expenditure.

CONCLUSION:

Thus, within the PVN, NPY stimulates the release of endocannabinoids and NO via Ca2+-influx from the endoplasmic reticulum. Both transmitter systems appear to have unique roles in the mediation of the NPY-induced regulation of energy homeostasis, suggesting that NPY regulates food intake, energy expenditure, and locomotor activity through different neuronal networks of this nucleus.

KEYWORDS:

Endocannabinoid; Hypothalamic paraventricular nucleus; NPY; Nitric oxide

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