Concomitant alpha7 and beta2 nicotinic AChR subunit deficiency leads to impaired energy homeostasis and increased physical activity in mice

• Published in: Molecular genetics and metabolism 2014-05, Vol.112 (1), p.64-72
• Main Authors: Somm, Emmanuel, Guérardel, Audrey, Maouche, Kamel, Toulotte, Audrey, Veyrat-Durebex, Christelle, Rohner-Jeanrenaud, Françoise, Maskos, Uwe, Hüppi, Petra S., Schwitzgebel, Valérie M.
• Format: Article
• Language: English
• Subjects: Adipocyte; Adipose Tissue; Adipose Tissue - metabolism; Animals; Cognitive science; Diabetes; Glucose; Glucose - metabolism; Glycemic Index; Humans; Insulin; Insulin - metabolism; Insulin Secretion; Islet; Islets of Langerhans; Islets of Langerhans - metabolism; Life Sciences; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; nAChR; Neuroscience; Obesity; Receptors, Nicotinic; Receptors, Nicotinic - genetics; Receptors, Nicotinic - metabolism
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2014.03.003

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. •α7 and β2 were the nAChR subunits most predominantly expressed in mice pancreatic islets but at a lower level than in central structures.•α7β2nAChR−/− mice present dampened basal glycemia but no change in insulin secretion and insulin sensitivity.•α7β2nAChR−/− mice present normal body weight, slight hyperphagia and decreased fat pad weight.•This lean phenotype can be explained by an increase in spontaneous physical activity observed in α7β2nAChR−/− mice possibly due to nAChR deficiency in central structures.