title: Concomitant alpha7 and beta2 nicotinic AChR subunit deficiency leads to impaired energy homeostasis and increased physical activity in mice.
abstract: Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels well characterized in neuronal signal transmission. Moreover, recent studies have revealed nAChR expression in nonneuronal cell types throughout the body, including tissues involved in metabolism. In the present study, we screen gene expression of nAChR subunits in pancreatic islets and adipose tissues. Mice pancreatic islets present predominant expression of α7 and β2 nAChR subunits but at a lower level than in central structures. Characterization of glucose and energy homeostasis in α7β2nAChR(-/-) mice revealed no major defect in insulin secretion and sensitivity but decreased glycemia apparently unrelated to gluconeogenesis or glycogenolysis. α7β2nAChR(-/-) mice presented an increase in lean and bone body mass and a decrease in fat storage with normal body weight. These observations were associated with elevated spontaneous physical activity in α7β2nAChR(-/-) mice, mainly due to elevation in fine vertical (rearing) activity while their horizontal (ambulatory) activity remained unchanged. In contrast to α7nAChR(-/-) mice presenting glucose intolerance and insulin resistance associated to excessive inflammation of adipose tissue, the present metabolic phenotyping of α7β2nAChR(-/-) mice revealed a metabolic improvement possibly linked to the increase in spontaneous physical activity related to central β2nAChR deficiency.
authors.affiliation: Division of Development and Growth, Department of Paediatrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: emmanuel.somm@chuv.ch.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Somm
authors.affiliation: Division of Development and Growth, Department of Paediatrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Audrey
authors.initials: A
authors.lastname: Guérardel
authors.affiliation: Université Paris-Diderot, Sorbonne-Paris-Cité, Laboratoire B2PE (Biologie et Pathologie du Pancréas Endocrine), Unité BFA (Biologie Fonctionnelle et Adaptative), CNRS UMR 8251, Paris, France.
authors.forename: Kamel
authors.initials: K
authors.lastname: Maouche
authors.affiliation: Division of Development and Growth, Department of Paediatrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Audrey
authors.initials: A
authors.lastname: Toulotte
authors.affiliation: Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Christelle
authors.initials: C
authors.lastname: Veyrat-Durebex
authors.affiliation: Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Françoise
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
authors.affiliation: Département de Neuroscience, Institut Pasteur, Unité Neurobiologie intégrative des systèmes cholinergiques, Paris, France.
authors.forename: Uwe
authors.initials: U
authors.lastname: Maskos
authors.affiliation: Division of Development and Growth, Department of Paediatrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Petra S
authors.initials: PS
authors.lastname: Hüppi
authors.affiliation: Division of Development and Growth, Department of Paediatrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Valérie M
authors.initials: VM
authors.lastname: Schwitzgebel
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D038321:Glycemic Index; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D011978:Receptors, Nicotinic; D005947:Glucose
keywords: Adipocyte; Diabetes; Islet; Obesity; nAChR