title: The K+ channel TASK1 modulates β-adrenergic response in brown adipose tissue through the mineralocorticoid receptor pathway.
abstract: Brown adipose tissue (BAT) is essential for adaptive thermogenesis and dissipation of caloric excess through the activity of uncoupling protein (UCP)-1. BAT in humans is of great interest for the treatment of obesity and related diseases. In this study, the expression of Twik-related acid-sensitive K(+) channel (TASK)-1 [a pH-sensitive potassium channel encoded by the potassium channel, 2-pore domain, subfamily K, member 3 (Kcnk3) gene] correlated highly with Ucp1 expression in obese and cold-exposed mice. In addition, Task1-null mice, compared with their controls, became overweight, mainly because of an increase in white adipose tissue mass and BAT whitening. Task1(-/-)-mouse-derived brown adipocytes, compared with wild-type mouse-derived brown adipocytes, displayed an impaired β3-adrenergic receptor response that was characterized by a decrease in oxygen consumption, Ucp1 expression, and lipolysis. This phenotype was thought to be caused by an exacerbation of mineralocorticoid receptor (MR) signaling, given that it was mimicked by corticoids and reversed by an MR inhibitor. We concluded that the K(+) channel TASK1 controls the thermogenic activity in brown adipocytes through modulation of β-adrenergic receptor signaling.
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Didier F
authors.initials: DF
authors.lastname: Pisani
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Guillaume E
authors.initials: GE
authors.lastname: Beranger
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Alain
authors.initials: A
authors.lastname: Corinus
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Maude
authors.initials: M
authors.lastname: Giroud
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Rayane A
authors.initials: RA
authors.lastname: Ghandour
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Jordi
authors.initials: J
authors.lastname: Altirriba
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Chambard
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Mazure
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Saïd
authors.initials: S
authors.lastname: Bendahhou
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Christophe
authors.initials: C
authors.lastname: Duranton
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Michiels
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: Frontini
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Françoise
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Christian
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom amri@unice.fr jacques.barhanin@unice.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Barhanin
authors.affiliation: *University of Nice Sophia Antipolis, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (iBV), Unité Mixte de Recherche (UMR) 7277, Nice, France; U1091, iBV, INSERM, Nice, France; UMR 7370 and Laboratories of Excellence, Ion Channel Science and Therapeutics, Laboratoire de PhysioMédecine Moléculaire (LP2M), CNRS, Nice, France; Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland, UMR 7284 and **U1081, CNRS, Institute for Research in Cancer and Aging in Nice, INSERM, Nice, France; Anatomopathology Service, Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France; Obesity Center, Department of Experimental and Clinical Medicine, Ancona, Italy; Warwick Medical School, University of Warwick, Coventry, United Kingdom amri@unice.fr jacques.barhanin@unice.fr.
authors.forename: Ez-Zoubir
authors.initials: EZ
authors.lastname: Amri
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D022722:Thermogenesis / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D022702:Receptors, Adrenergic, beta-3; D018161:Receptors, Mineralocorticoid; C420132:potassium channel subfamily K member 3
keywords: KCNK3; UCP1; aldosterone; obesity; thermogenesis