Regulation by Na-K pump of glucose-sensitive NPY neurons and feeding behavior, and its dysfunction in hyperphagia and obesity

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In the glucose-sensitive neurons (GSNs) in the hypothalamic arcuate nucleus (ARC), lowering glucose concentration increases cytosolic Na+ concentration ([Na+]) that is inhibited by activator of Na,K-ATPase (NKA), SSA412. The results indicate that suppression of NKA is implicated in the response to lowering glucose. The NKA suppression is mediated by decrease in intracellular ATP. The NKA suppression, possibly by inducing depolarization, activates voltage-dependent Ca channels and increases [Ca2+]. Pharmacologic inhibition of NKA increases neuropeptide Y (NPY) mRNA expression and food intake.In ARC GSNs, lowering glucose, via intracellular ATP reduction, causes NKA suppression, which activates NPY neurons to promote feeding.