K(ATP)-channel-dependent regulation of catecholaminergic neurons controls BAT sympathetic nerve activity and energy homeostasis.
| Autor: | Tovar S; Department of Mouse Genetics and Metabolism, Institute for Genetics and Center for Molecular Medicine (CMMC), University of Cologne, Zülpicher Strasse 47b, 50674 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Zülpicher Strasse 47b, 50674 Cologne, Germany; Max Planck Institute for Neurological Research, Gleueler Strasse 50, 50931 Cologne, Germany., Paeger L, Hess S, Morgan DA, Hausen AC, Brönneke HS, Hampel B, Ackermann PJ, Evers N, Büning H, Wunderlich FT, Rahmouni K, Kloppenburg P, Brüning JC |
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| Jazyk: | angličtina |
| Zdroj: | Cell metabolism [Cell Metab] 2013 Sep 03; Vol. 18 (3), pp. 445-55. |
| DOI: | 10.1016/j.cmet.2013.08.006 |
| Abstrakt: | 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. (Copyright © 2013 Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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