Universität zu Köln

Steculorum, Sophie Marie, Timper, Katharina, Ruud, Linda Engstroem, Evers, Nadine, Paeger, Lars ORCID: 0000-0001-8716-3483, Bremser, Stephan, Kloppenburg, Peter and Bruening, Jens Claus (2017). Inhibition of P2Y6 Signaling in AgRP Neurons Reduces Food Intake and Improves Systemic Insulin Sensitivity in Obesity. Cell Reports, 18 (7). S. 1587 - 1598. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Uridine-diphosphate (UDP) and its receptor P2Y6 have recently been identified as regulators of AgRP neurons. UDP promotes feeding via activation of P2Y6 receptors on AgRP neurons, and hypothalamic UDP concentrations are increased in obesity. However, it remained unresolved whether inhibition of P2Y6 signaling pharmacologically, globally, or restricted to AgRP neurons can improve obesity-associated metabolic dysfunctions. Here, we demonstrate that central injection of UDP acutely promotes feeding in diet-induced obese mice and that acute pharmacological blocking of CNS P2Y6 receptors reduces food intake. Importantly, mice with AgRP-neuron-restricted inactivation of P2Y6 exhibit reduced food intake and fat mass as well as improved systemic insulin sensitivity with improved insulin action in liver. Our results reveal that P2Y6 signaling in AgRP neurons is involved in the onset of obesity-associated hyperphagia and systemic insulin resistance. Collectively, these experiments define P2Y6 as a potential target to pharmacologically restrict both feeding and systemic insulin resistance in obesity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Steculorum, Sophie Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Timper, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruud, Linda Engstroem UNSPECIFIED UNSPECIFIED UNSPECIFIED Evers, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Paeger, Lars UNSPECIFIED orcid.org/0000-0001-8716-3483 UNSPECIFIED Bremser, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloppenburg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-239780
DOI:	10.1016/j.celrep.2017.01.047
Journal or Publication Title:	Cell Reports
Volume:	18
Number:	7
Page Range:	S. 1587 - 1598
Date:	2017
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXPRESSING NEURONS; ADIPOSE-TISSUE; ENERGY-BALANCE; BRAIN-SLICES; BODY-WEIGHT; RESISTANCE; LEPTIN; MICE; HOMEOSTASIS; ACTIVATION Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23978