title: K(ATP)-channel-dependent regulation of catecholaminergic neurons controls BAT sympathetic nerve activity and energy homeostasis.
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.
authors.affiliation: 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.
authors.forename: Sulay
authors.initials: S
authors.lastname: Tovar
authors.forename: Lars
authors.initials: L
authors.lastname: Paeger
authors.forename: Simon
authors.initials: S
authors.lastname: Hess
authors.forename: Donald A
authors.initials: DA
authors.lastname: Morgan
authors.forename: A Christine
authors.initials: AC
authors.lastname: Hausen
authors.forename: Hella S
authors.initials: HS
authors.lastname: Brönneke
authors.forename: Brigitte
authors.initials: B
authors.lastname: Hampel
authors.forename: P Justus
authors.initials: PJ
authors.lastname: Ackermann
authors.forename: Nadine
authors.initials: N
authors.lastname: Evers
authors.forename: Hildegard
authors.initials: H
authors.lastname: Büning
authors.forename: F Thomas
authors.initials: FT
authors.lastname: Wunderlich
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
authors.forename: Peter
authors.initials: P
authors.lastname: Kloppenburg
authors.forename: Jens C
authors.initials: JC
authors.lastname: Brüning
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D059329:Cholinergic Neurons / Q000187:drug effects / Q000378:metabolism*; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000099161:Kcnj11 Channel
chemical_list: D005947:Glucose; D024661:Potassium Channels, Inwardly Rectifying; D014446:Tyrosine 3-Monooxygenase; D000099161:Kcnj11 Channel