Nicotinic cholinergic signaling in adipose tissue and pancreatic islets biology: revisited function and therapeutic perspectives

Abstract

Nicotinic acetylcholine receptors (nAChRs) are membrane ligand-gated cation channels whose activation is triggered by the binding of the endogenous neurotransmitter acetylcholine or other biologic compounds including nicotine. Their roles in synaptic transmission in the central and peripheral nervous system as well as in the neuromuscular junction have been extensively studied. Recent implications of nAChRs in intracellular signaling and their detection in peripheral nonneural cells (including epithelial cells and immune cells) have renewed the interest for this class of ionotropic receptors. In the present review, we focus our attention on the potential use of nicotinic cholinergic signaling in the treatment of metabolic diseases (such as obesity and diabetes) in browsing functions of nAChRs in adipose tissue and pancreatic islet biology. In fact, different nAChR subunits can be detected in these metabolic tissues, as well as in immune cells interacting with them. Various rodent models of obesity and diabetes benefit from stimulation of the nicotinic cholinergic pathway, whereas mice deficient for some nAChRs, in particular the α7 nAChR subunit, harbor a worsened metabolic phenotype. In contrast to potential therapeutic applications in metabolic diseases, an overstimulation of this signaling pathway during the early stage of development (typically through nicotine exposure during fetal life) presents deleterious consequences on ontogeny and functionality of adipose tissue and the endocrine pancreas which persist throughout life.