title: 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.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.|Department of Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Science, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Bruinstroop
authors.affiliation: Department of Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Science, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Eliveld
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.|Department of Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Science, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Foppen
authors.affiliation: Department of Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Science, Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Busker
authors.affiliation: Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Ackermans
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.|Department of Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Science, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Kalsbeek
mesh_terms: D000818:Animals; D003714:Denervation; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000294:innervation* / Q000378:metabolism; D009765:Obesity / Q000473:pathology*; D051381:Rats; D011924:Rats, Zucker; D013564:Sympathetic Nervous System / Q000473:pathology*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride