Direct Stimulation of Ghrelin Secretion by Sympathetic Nerves

Abstract

The hormone ghrelin is secreted mainly from the gut, rises in peripheral plasma before meals, and is implicated in stimulating hunger, initiating meals, and developing obesity. We hypothesize that activation of the sympathetic nervous system contributes to preprandial ghrelin surges. The present studies in isoflurane-anesthetized Wistar rats were designed to determine whether sympathetic nerves and neurohormones are capable of stimulating ghrelin secretion. We activated gut sympathetic nerves by two methods: electrical sympathetic nerve stimulation (SNS) and chemical sympathetic nerve activation with iv tyramine (TYR) administration. Portal venous blood was sampled before and during a 10-min sympathetic stimulation. Successful activation of gut sympathetic nerves was verified by increments in portal venous norepinephrine. SNS increased portal ghrelin by 206 +/- 50%. In contrast, simply isolating gut sympathetic nerves without applying current had a minimal effect on ghrelin levels. TYR also increased portal ghrelin [change (Delta), +52 +/- 11%], whereas saline infusion had little effect. We next determined whether the neural stimulation of ghrelin secretion was mediated indirectly via the suppression of insulin secretion during SNS and TYR. Streptozotocin-induced diabetes prevented a fall in insulin during TYR, yet the portal ghrelin response (Delta = +47 +/- 18%) was similar to that in nondiabetic rats. Lastly, to test for humoral stimulation of ghrelin, we infused the sympathetic neurohormone, epinephrine, to achieve levels found during severe stress. Epinephrine failed to stimulate ghrelin secretion (Delta = +4 +/- 35%). We conclude that the neural, but not the neurohumoral, branch of the sympathetic nervous system can directly stimulate ghrelin secretion.