Total energy expenditure, adjusted for body weight, was significantly associated with rs12104221 in MATK which encodes a protein-tyrosine kinase involved in signal transduction pathways [54]. Sleeping energy expenditure, adjusted for body weight, was associated with rs8040868 in CHRNA3 (cholinergic receptor, neuronal nicotinic, alpha polypeptide 3), a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. After binding to acetylcholine, the receptor responds by opening ion-conducting channels across the plasma membrane, suggesting a plausible role of the coding variant (rs8040868) in energy metabolism [55]. Acetylcholine receptors activate proopiomelanocortin neurons that in turn activate melanocortin-4 receptors that are involved in the regulation of energy intake and expenditure [56], [57].
