Isolated Hepatic Cholinergic Denervation Impairs Glucose and Glycogen Metabolism

Cheng, Xue; Aspelund, Gudrun; Sritharan, Kumudesh C.; Wang, Jin Ping; Slezak, Lori A.; Andersen, Dana K.

doi:10.1006/jsre.2000.5820

Cited by 36 publications

(24 citation statements)

References 17 publications

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“…Next to a direct effect of the autonomic nervous system on lipid metabolism, it is possible that parasympathetic activity increases insulin sensitivity of the liver. We did not find an effect of a parasympathetic denervation on plasma concentrations of glucose or insulin, but previous studies using several methods to measure insulin sensitivity found decreased insulin sensitivity after parasympathetic denervation (19,22,37,38). Despite stimulating hepatic fatty acid and TG synthesis, which are substrates for VLDL-TG secretion, acute elevations of insulin are known to inhibit VLDL-TG secretion (20).…”

Section: Discussionmentioning

confidence: 41%

“…Nevertheless, the role of hepatic autonomic nerves under physiological conditions has often been debated since no gross abnormality of metabolic homeostasis was observed after interruption of the nervous supply to the liver. However, effects of a selective parasympathetic denervation on hepatic glucose production, glycogen synthesis, and hepatic insulin sensitivity were reported, pointing to a possible fast route to fine-tune metabolism in addition to the direct regulation by nutrients and hormones (19,22,37,38). Interestingly, the effects of parasympathetic hepatic denervation were most obvious in the postprandial state, indicating that feeding activates the parasympathetic nervous system.…”

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confidence: 99%

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The autonomic nervous system regulates postprandial hepatic lipid metabolism

Bruinstroop

Fleur

Ackermans

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Bruinstroop E, la Fleur SE, Ackermans MT, Foppen E, Wortel J, Kooijman S, Berbée JF, Rensen PC, Fliers E, Kalsbeek A. The autonomic nervous system regulates postprandial hepatic lipid metabolism. Am J Physiol Endocrinol Metab 304: E1089 -E1096, 2013. First published March 26, 2013; doi:10.1152/ajpendo.00614.2012The liver is a key organ in controlling glucose and lipid metabolism during feeding and fasting. In addition to hormones and nutrients, inputs from the autonomic nervous system are also involved in fine-tuning hepatic metabolic regulation. Previously, we have shown in rats that during fasting an intact sympathetic innervation of the liver is essential to maintain the secretion of triglycerides by the liver. In the current study, we hypothesized that in the postprandial condition the parasympathetic input to the liver inhibits hepatic VLDL-TG secretion. To test our hypothesis, we determined the effect of selective surgical hepatic denervations on triglyceride metabolism after a meal in male Wistar rats. We report that postprandial plasma triglyceride concentrations were significantly elevated in parasympathetically denervated rats compared with control rats (P ϭ 0.008), and VLDL-TG production tended to be increased (P ϭ 0.066). Sympathetically denervated rats also showed a small rise in postprandial triglyceride concentrations (P ϭ 0.045). On the other hand, in rats fed on a six-meals-a-day schedule for several weeks, a parasympathetic denervation resulted in Ͼ70% higher plasma triglycerides during the day (P ϭ 0.001), whereas a sympathetic denervation had no effect. Our results show that abolishing the parasympathetic input to the liver results in increased plasma triglyceride levels during postprandial conditions. parasympathetic; denervation; liver; triglycerides; feeding THE LIVER IS ESSENTIAL for maintaining metabolic equilibrium in the body by storing and releasing large quantities of energy according to changing demands. In the postprandial state the liver plays a central role in storing energy for later use, whereas in the fasted state the liver increases fuel availability for immediate use. These processes are controlled by circulating hormones, such as insulin, and by the availability of different nutrients. It has long been known that the autonomic nervous input to the liver can also alter hepatic function, especially glucose metabolism (27, 28). Next to being a key player in glucose metabolism, the liver is also important for the regulation of lipid metabolism, as it synthesizes and degrades lipids. Recently, various investigators have revealed a role for the autonomic nervous system in the regulation of hepatic lipid metabolism as well (6,18,32).The autonomic nervous system consists of a sympathetic and a parasympathetic branch. Tracing studies have shown that both branches are anatomically connected to the liver and originate from distinct neuronal populations within the hypothalamus (7,17,35). The two autonomic branches are hypothesized to have opposing or complimentary effects on target org...

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Section: Discussionmentioning

confidence: 41%

mentioning

confidence: 99%

The autonomic nervous system regulates postprandial hepatic lipid metabolism

Bruinstroop

Fleur

Ackermans

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…Moreover, both the studies of Chap et al (6) and Shiota et al (42) suffer from the fact that it is difficult to be sure that neurotransmitters or receptor blocking agents reach their physiological targets when they are delivered via the bloodstream, as previously noted in regard to the NE infusion in the current study. In regard to surgical interruption of vagal signaling, it is noteworthy that rats with isolated hepatic cholinergic denervation exhibited significantly less hepatic glycogen in the fed state than did sham-operated controls (45). However, the rats were studied 4 wk postoperatively.…”

Section: Role Of Parasympathetic Innervation In Liver Glucose Metabolismmentioning

confidence: 99%

Vagal cooling and concomitant portal norepinephrine infusion do not reduce net hepatic glucose uptake in conscious dogs

Cardin¹,

Pagliassotti²,

Moore³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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We examined the role of efferent neural signaling in regulation of net hepatic glucose uptake (NHGU) in two groups of conscious dogs with hollow perfusable coils around their vagus nerves, using tracer and arteriovenous difference techniques. Somatostatin, intraportal insulin and glucagon at fourfold basal and basal rates, and intraportal glucose at 3.8 mg.kg(-1).min(-1) were infused continuously. From 0 to 90 min [period 1 (P1)], the coils were perfused with a 37 degrees C solution. During period 2 [P2; 90-150 min in group 1 (n = 3); 90-180 min in group 2 (n = 6)], the coils were perfused with -15 degrees C solution to eliminate vagal signaling, and the coils were subsequently perfused with 37 degrees C solution during period 3 (P3). In addition, group 2 received an intraportal infusion of norepinephrine at 16 ng.kg(-1).min(-1) during P2. The effectiveness of vagal suppression was demonstrated by the increase in heart rate during P2 (111 +/- 17, 167 +/- 16, and 105 +/- 13 beats/min in group 1 and 71 +/- 6, 200 +/- 11, and 76 +/- 6 beats/min in group 2 during P1-P3, respectively) and by prolapse of the third eyelid during P2. Arterial plasma glucose, insulin, and glucagon concentrations; hepatic blood flow; and hepatic glucose load did not change significantly during P1-P3. NHGU during P1-P3 was 2.7 +/- 0.4, 4.1 +/- 0.6, and 4.0 +/- 1.2 mg.kg(-1).min(-1) in group 1 and 5.0 +/- 0.9, 5.6 +/- 0.7, and 6.1 +/- 0.9 mg.kg(-1).min(-1) in group 2 (not significant among periods). Interruption of vagal signaling with or without intraportal infusion of norepinephrine to augment sympathetic tone did not suppress NHGU during portal glucose delivery, suggesting the portal signal stimulates NHGU independently of vagal efferent flow.

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“…From available measurements of rates of oxygen consumption, ATP utilization, and glucose uptake and output during glycogenic and glycogenolytic stimulation in the perfused rat liver (12,16,34), the reaction fluxes through the metabolic Fig. 1.…”

Section: Identification Of Hepatic Cell Fluxesmentioning

confidence: 99%

Thermodynamic-based computational profiling of cellular regulatory control in hepatocyte metabolism

Beard

Qian

2005

American Journal of Physiology-Endocrinology and Metabolism

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Beard, Daniel A., and Hong Qian. Thermodynamic-based computational profiling of cellular regulatory control in hepatocyte metabolism. Am J Physiol Endocrinol Metab 288: E633-E644, 2005. First published October 26, 2004; doi:10.1152/ajpendo.00239.2004.-Thermodynamic-based constraints on biochemical fluxes and concentrations are applied in concert with mass balance of fluxes in glycogenesis and glycogenolysis in a model of hepatic cell metabolism. Constraint-based modeling methods that facilitate predictions of reactant concentrations, reaction potentials, and enzyme activities are introduced to identify putative regulatory and control sites in biological networks by computing the minimal control scheme necessary to switch between metabolic modes. Computational predictions of control sites in glycogenic and glycogenolytic operational modes in the hepatocyte network compare favorably with known regulatory mechanisms. The developed hepatic metabolic model is used to computationally analyze the impairment of glucose production in von Gierke's and Hers' diseases, two metabolic diseases impacting glycogen metabolism. The computational methodology introduced here can be generalized to identify downstream targets of agonists, to systematically probe possible drug targets, and to predict the effects of specific inhibitors (or activators) on integrated network function. network thermodynamics; nonequilibrium steady state; biochemical network CONSTRAINT-BASED APPROACHES to modeling biochemical systems provide powerful computational tools for predicting the metabolic capabilities of whole genome cell systems (14,15,(17)(18)(19)). Yet, the most widely used computational method for large-scale systems, flux-balance analysis (FBA), typically cannot provide precise predictions of biochemical fluxes. Rather, FBA uses the known network stoichiometry to impose a steady-state mass balance constraint that yields a feasible flux space within which an infinite number of equivalent solutions can exist (13,29,32). The recently introduced theory of energy-balance analysis (EBA) augments FBA by characterizing the thermodynamic constraints on reaction-free energies that arise from the network stoichiometry (8,9,28). This theory provides the framework for introducing thermodynamic constraints into biochemical network modeling, but still does not identify enough constraints to provide reliable estimates of free energies, concentrations, and fluxes for a whole cell system, a problem of intense current interest.In this work, physicochemical constraints on metabolite concentrations are incorporated into FBA and EBA, and these tools are applied to understanding metabolic regulation in the hepatocyte. Application of these constraints, which arise naturally from reaction thermodynamics, provide modeling results that 1) are more physically realistic and biologically meaningful than are provided by FBA alone, 2) facilitate direct comparison of computational predictions and experimental results, and 3) reveal insight into the regulatory and control me...

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Isolated Hepatic Cholinergic Denervation Impairs Glucose and Glycogen Metabolism

Cited by 36 publications

References 17 publications

The autonomic nervous system regulates postprandial hepatic lipid metabolism

The autonomic nervous system regulates postprandial hepatic lipid metabolism

Vagal cooling and concomitant portal norepinephrine infusion do not reduce net hepatic glucose uptake in conscious dogs

Thermodynamic-based computational profiling of cellular regulatory control in hepatocyte metabolism

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