Universität zu Köln

Tovar, Sulay ORCID: 0000-0001-7813-6520, Paeger, Lars ORCID: 0000-0001-8716-3483, Hess, Simon, Morgan, Donald A., Hausen, A. Christine, Broenneke, Hella S., Hampel, Brigitte, Ackermann, P. Justus, Evers, Nadine, Buening, Hildegard, Wunderlich, F. Thomas, Rahmouni, Kamal ORCID: 0000-0001-5136-6748, Kloppenburg, Peter and Bruening, Jens C. (2013). K-ATP-Channel-Dependent Regulation of Catecholaminergic Neurons Controls BAT Sympathetic Nerve Activity and Energy Homeostasis. Cell Metab., 18 (3). S. 445 - 456. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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Abstract

Brown adipose tissue (BAT) is a critical regulator of glucose, lipid, and energy homeostasis, and its activity is tightly controlled by the sympathetic nervous system. However, the mechanisms underlying CNS-dependent control of BAT sympathetic nerve activity (SNA) are only partly understood. Here, we demonstrate that catecholaminergic neurons in the locus coeruleus (LC) adapt their firing frequency to extracellular glucose concentrations in a K-ATP-channel-dependent manner. Inhibiting K-ATP-channel-dependent control of neuronal activity via the expression of a variant K-ATP channel in tyrosine-hydroxylase-expressing neurons and in neurons of the LC enhances diet-induced obesity in mice. Obesity results from decreased energy expenditure, lower steady-state BAT SNA, and an attenuated ability of centrally applied glucose to activate BAT SNA. This impairs the thermogenic transcriptional program of BAT. Collectively, our data reveal a role of K-ATP-channel-dependent neuronal excitability in catecholaminergic neurons in maintaining thermogenic BAT sympathetic tone and energy homeostasis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tovar, Sulay UNSPECIFIED orcid.org/0000-0001-7813-6520 UNSPECIFIED Paeger, Lars UNSPECIFIED orcid.org/0000-0001-8716-3483 UNSPECIFIED Hess, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Morgan, Donald A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hausen, A. Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Broenneke, Hella S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hampel, Brigitte UNSPECIFIED UNSPECIFIED UNSPECIFIED Ackermann, P. Justus UNSPECIFIED UNSPECIFIED UNSPECIFIED Evers, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Buening, Hildegard UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, F. Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Rahmouni, Kamal UNSPECIFIED orcid.org/0000-0001-5136-6748 UNSPECIFIED Kloppenburg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-476128
DOI:	10.1016/j.cmet.2013.08.006
Journal or Publication Title:	Cell Metab.
Volume:	18
Number:	3
Page Range:	S. 445 - 456
Date:	2013
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1932-7420
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BROWN ADIPOSE-TISSUE; NORADRENERGIC LOCUS-COERULEUS; OBESE ZUCKER RATS; VENTROLATERAL MEDULLA; FUNCTIONAL NEUROANATOMY; EFFERENT NERVES; GLUCOSE; THERMOGENESIS; INSULIN; ROLES Multiple languages Cell Biology; Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47612