The autonomic nervous system regulates postprandial hepatic lipid metabolism

Bruinstroop, Eveline; Fleur, Susanne E. la; Ackermans, Mariëtte T.; Foppen, Ewout; Wortel, Joke; Kooijman, Sander; Berbée, Jimmy F.P.; Rensen, Patrick C.N.; Fliers, Eric; Kalsbeek, Andries

doi:10.1152/ajpendo.00614.2012

Cited by 32 publications

(19 citation statements)

References 38 publications

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“…A second hypothesis is the effect of denervating the liver. This hypothesis has been studied in animal models, showing that parasympathetic denervation results on changes in diet consumption, hypertriglyceridemia, IR, and hypercholesterolemia …”

Section: Discussionmentioning

confidence: 99%

Long‐term outcomes of patients undergoing simultaneous liver transplantation and sleeve gastrectomy

Zamora-Valdés¹,

Watt²,

Kellogg³

et al. 2018

Hepatology

118

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Section: Discussionmentioning

confidence: 99%

Long‐term outcomes of patients undergoing simultaneous liver transplantation and sleeve gastrectomy

Zamora-Valdés¹,

Watt²,

Kellogg³

et al. 2018

Hepatology

118

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“…12 We tested our hypothesis in obese (fa/fa) Zucker rats by measuring plasma TG levels and hepatic VLDL-TG secretion during a timeframe of 6 weeks after a surgical sympathetic or parasympathetic denervation of the liver.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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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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“…Anatomical studies have shown that the sympathetic and parasympathetic connections to the liver originate from different brain regions within the hypothalamus and the brainstem . Within the hypothalamus, the paraventricular, arcuate, and suprachiasmatic nuclei as well as the lateral hypothalamic area (LHA) project and modulate liver metabolism …”

mentioning

confidence: 99%

Hypothalamic kappa opioid receptor mediates both diet‐induced and melanin concentrating hormone–induced liver damage through inflammation and endoplasmic reticulum stress

et al. 2016

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The opioid system is widely known to modulate the brain reward system and thus affect the behavior of humans and other animals, including feeding. We hypothesized that the hypothalamic opioid system might also control energy metabolism in peripheral tissues. Mice lacking the kappa opioid receptor (κOR) and adenoviral vectors overexpressing or silencing κOR were stereotaxically delivered in the lateral hypothalamic area (LHA) of rats. Vagal denervation was performed to assess its effect on liver metabolism. Endoplasmic reticulum (ER) stress was inhibited by pharmacological (tauroursodeoxycholic acid) and genetic (overexpression of the chaperone glucose‐regulated protein 78 kDa) approaches. The peripheral effects on lipid metabolism were assessed by histological techniques and western blot. We show that in the LHA κOR directly controls hepatic lipid metabolism through the parasympathetic nervous system, independent of changes in food intake and body weight. κOR colocalizes with melanin concentrating hormone receptor 1 (MCH‐R1) in the LHA, and genetic disruption of κOR reduced melanin concentrating hormone–induced liver steatosis. The functional relevance of these findings was given by the fact that silencing of κOR in the LHA attenuated both methionine choline–deficient, diet‐induced and choline‐deficient, high‐fat diet–induced ER stress, inflammation, steatohepatitis, and fibrosis, whereas overexpression of κOR in this area promoted liver steatosis. Overexpression of glucose‐regulated protein 78 kDa in the liver abolished hypothalamic κOR‐induced steatosis by reducing hepatic ER stress. Conclusions: This study reveals a novel hypothalamic–parasympathetic circuit modulating hepatic function through inflammation and ER stress independent of changes in food intake or body weight; these findings might have implications for the clinical use of opioid receptor antagonists. (Hepatology 2016;64:1086‐1104)

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The autonomic nervous system regulates postprandial hepatic lipid metabolism

Cited by 32 publications

References 38 publications

Long‐term outcomes of patients undergoing simultaneous liver transplantation and sleeve gastrectomy

Long‐term outcomes of patients undergoing simultaneous liver transplantation and sleeve gastrectomy

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

Hypothalamic kappa opioid receptor mediates both diet‐induced and melanin concentrating hormone–induced liver damage through inflammation and endoplasmic reticulum stress

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