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Hepatic denervation and dyslipidemia in obese Zucker (fa/fa) rats

Abstract

Human and animal studies increasingly point toward a neural pathogenesis of the metabolic syndrome, involving hypothalamic and autonomic nervous system dysfunction. We hypothesized that increased very-low-density lipoprotein−triglyceride (VLDL–TG) secretion by the liver in a rat model for dyslipidemia, that is, the obese Zucker (fa/fa) rat, is due to relative hyperactivity of sympathetic, and/or hypoactivity of parasympathetic hepatic innervation. To test the involvement of the autonomic nervous system, we surgically denervated the sympathetic or parasympathetic hepatic nerve in obese Zucker rats. Our results show that cutting the sympathetic hepatic nerve lowers VLDL–TG secretion in obese rats, finally resulting in lower plasma TG concentrations after 6 weeks. In contrast, a parasympathetic denervation results in increased plasma total cholesterol concentrations. The effect of a sympathetic or parasympathetic denervation of the liver was independent of changes in humoral factors or changes in body weight or food intake. In conclusion, a sympathetic denervation improves the lipid profile in obese Zucker rats, whereas a parasympathetic denervation increases total cholesterol levels. We believe this is a novel treatment target, which should be further investigated.

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Acknowledgements

This work is supported by NWO-ZonMw (TOP 91207036). We thank Emmely de Vries, Merel Rijnsburger and Rianne van der Spek, from the Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam; Marja Neeleman from the Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center (AMC), University of Amsterdam, and Sander Houten and Simone Denis from the Laboratory Genetic Metabolic Diseases, Academic Medical Center (AMC), University of Amsterdam, for experimental assistance.

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Correspondence to E Bruinstroop.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Bruinstroop, E., Eliveld, J., Foppen, E. et al. Hepatic denervation and dyslipidemia in obese Zucker (fa/fa) rats. Int J Obes 39, 1655–1658 (2015). https://doi.org/10.1038/ijo.2015.122

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