The Constitutive Lack of α7 Nicotinic Receptor Leads to Metabolic Disorders in Mouse

Blandine Gausserès (1) , Junjun Liu (1) , Ewout Foppen (1) , Cécile Tourrel-Cuzin (1) , Ana Rodriguez Sanchez-Archidona (2) , Etienne Delangre (1) , Céline Cruciani-Guglielmacci (1) , Stéphanie Pons (3) , Uwe Maskos (3) , Bernard Thorens (2) , Christophe Magnan (1) , Jamileh Movassat (1) , Kamel Maouche (1)

1 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative
2 CIG - Center for Integrative Genomics - Institute of Bioinformatics, Génopode
3 NISC - Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems

Objective: Type 2 diabetes (T2D) occurs by deterioration in pancreatic β-cell function and/or progressive loss of pancreatic β-cell mass under the context of insulin resistance. α7 nicotinic acetylcholine receptor (nAChR) may contribute to insulin sensitivity but its role in the pathogenesis of T2D remains undefined. We investigated whether the systemic lack of α7 nAChR was sufficient to impair glucose homeostasis. Methods: We used an α7 nAChR knock-out (α7−/−) mouse model fed a standard chow diet. The effects of the lack of α7 nAChR on islet mass, insulin secretion, glucose and insulin tolerance, body composition, and food behaviour were assessed in vivo and ex vivo experiments. Results: Young α7−/− mice display a chronic mild high glycemia combined with an impaired glucose tolerance and a marked deficit in β-cell mass. In addition to these metabolic disorders, old mice developed adipose tissue inflammation, elevated plasma free fatty acid concentrations and presented glycolytic muscle insulin resistance in old mice. Finally, α7−/− mice, fed a chow diet, exhibited a late-onset excessive gain in body weight through increased fat mass associated with higher food intake. Conclusion: Our work highlights the important role of α7 nAChR in glucose homeostasis. The constitutive lack of α7 nAChR suggests a novel pathway influencing the pathogenesis of T2D.

Mots clés: α7 nAChR; β-cell mass; high glycemia; insulin resistance; fat mass

Domaines: Sciences cognitives

Blandine Gausserès, Junjun Liu, Ewout Foppen, Cécile Tourrel-Cuzin, Ana Rodriguez Sanchez-Archidona, et al.. The Constitutive Lack of α7 Nicotinic Receptor Leads to Metabolic Disorders in Mouse. Biomolecules, 2020, 10 (7), pp.1057. ⟨10.3390/biom10071057⟩. ⟨pasteur-02935951⟩