Hypothalamic neuropeptide Y controls the hepatic secretion of VLDL triglycerides in rats via the sympathetic nervous system
E Bruinstroop1, L Pei2,4, M Ackermans3, E Fliers1 & A Kalsbeek1,2
During fasting neuropeptide Y (NPY) neurons in the mediobasal hypothalamus are activated to increase food intake and to conserve energy. Under conditions of food deprivation, lipid metabolism plays an important role in providing fuel for muscle. We investigated if central NPY affects VLDL-TAG secretion directly via the autonomic nervous system. We measured VLDL-TAG secretion in Wistar rats by an intravenous bolus of tyloxapol to inhibit uptake of triglycerides by peripheral tissues. In the absence of chylomicrons from the gut, the increase in plasma triglycerides reflects VLDL-TAG secretion by the liver. First, we investigated the acute effect of i.c.v. infusion of NPY (1 μg/μl; bolus 5 μl/5 min, followed by 5 μl/h) on VLDL-TAG secretion after a selective sham or sympathetic liver denervation. Second, we investigated the effects of overnight fasting (19 h fast) in sham, parasympathetic, sympathetic, or total liver-denervated animals. Finally, we tested the effects of fasting and liver denervation in rats treated neonatally with monosodium glutamate (MSG), which is an established model for chronic NPY depletion from the arcuate nucleus. We report that hepatic sympathetic innervation mediates the stimulatory effect of i.c.v. NPY on VLDL-TAG secretion. During fasting, when hypothalamic NPY tone is physiologically high, an intact hepatic sympathetic innervation is necessary to maintain VLDL-TAG secretion. Finally, in MSG treated rats VLDL-TAG secretion could not be maintained during fasting while hepatic denervation did not yield any additional effect. Our findings show that the release of hypothalamic NPY during fasting stimulates triglyceride secretion by the liver via hepatic sympathetic input. By inference, an elevated hypothalamic NPY tone may increase sympathetic tone as well as plasma TAG in pathophysiological conditions such as the metabolic syndrome.