Universität zu Köln

Steculorum, Sophie M., Paeger, Lars ORCID: 0000-0001-8716-3483, Bremser, Stephan, Evers, Nadine, Hinze, Yvonne, Idzko, Marco, Kloppenburg, Peter and Bruening, Jens C. (2015). Hypothalamic UDP Increases in Obesity and Promotes Feeding via P2Y6-Dependent Activation of AgRP Neurons. Cell, 162 (6). S. 1404 - 1418. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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Abstract

Activation of orexigenic AgRP-expressing neurons in the arcuate nucleus of the hypothalamus potently promotes feeding, thus defining new regulators of AgRP neuron activity could uncover potential novel targets for obesity treatment. Here, we demonstrate that AgRP neurons express the purinergic receptor 6 (P2Y6), which is activated by uridine-diphosphate (UDP). In vivo, UDP induces ERK phosphorylation and cFos expression in AgRP neurons and promotes action potential firing of these neurons in brain slice recordings. Consequently, central application of UDP promotes feeding, and this response is abrogated upon pharmacologic or genetic inhibition of P2Y6 as well as upon pharmacogenetic inhibition of AgRP neuron activity. In obese animals, hypothalamic UDP content is elevated as a consequence of increased circulating uridine concentrations. Collectively, these experiments reveal a potential regulatory pathway in obesity, where peripheral uridine increases hypothalamic UDP concentrations, which in turn can promote feeding via PY6-dependent activation of AgRP neurons.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Steculorum, Sophie M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paeger, Lars UNSPECIFIED orcid.org/0000-0001-8716-3483 UNSPECIFIED Bremser, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Evers, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Hinze, Yvonne UNSPECIFIED UNSPECIFIED UNSPECIFIED Idzko, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloppenburg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-393075
DOI:	10.1016/j.cell.2015.08.032
Journal or Publication Title:	Cell
Volume:	162
Number:	6
Page Range:	S. 1404 - 1418
Date:	2015
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4172
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INSULIN-RESISTANCE; SYMPATHETIC NEURONS; ENERGY HOMEOSTASIS; EXPRESSING NEURONS; P2Y(6) RECEPTOR; URIDINE; LEPTIN; STIMULATION; BEHAVIOR; PROTEIN Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39307