Daily Rhythms in Metabolic Liver Enzymes and Plasma Glucose Require a Balance in the Autonomic Output to the Liver

Cailotto, Cathy; Heijningen, Caroline van; Vliet, Jan van der; Plasse, G; Habold, Caroline; Kalsbeek, Andries; Pévet, Paul; Buijs, Ruud M.

doi:10.1210/en.2007-0816

Cited by 87 publications

(49 citation statements)

References 41 publications

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“…Gardemann and Jungermann (13) showed that the effects of parasympathetic stimulation on glucose metabolism occurred only during concurrent ␣-and ␤-adrenergic blockade in perfused rat liver. In a previous experiment, we also observed that the effects of a parasympathetic or sympathetic denervation, i.e., a loss of the daily glucose rhythm, were not observed in animals with a total denervation (10). Together, these observations lead us to propose that it is not the absence but rather the disbalance of the autonomic nervous system that induces an abnormal metabolism in the liver.…”

Section: Discussionmentioning

confidence: 64%

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: 64%

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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“…The daily glucose oscillation peaks at the time of awakening mainly through increase in HGP (9,31). The balance between sympathetic and parasympathetic output to the liver is crucial for maintenance of the glucose rhythm (32), although the integrating mechanism has long been uncertain. We found that central action of orexin A at the awake period increased the amplitude of daily glucose oscillations via HGP in mice.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic Orexin Prevents Hepatic Insulin Resistance via Daily Bidirectional Regulation of Autonomic Nervous System in Mice

et al. 2014

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Circadian rhythm is crucial for preventing hepatic insulin resistance, although the mechanism remains uncovered. Here we report that the wake-active hypothalamic orexin system plays a key role in this regulation. Wildtype mice showed that a daily rhythm in blood glucose levels peaked at the awake period; however, the glucose rhythm disappeared in orexin knockout mice despite normal feeding rhythm. Central administration of orexin A during nighttime awake period acutely elevated blood glucose levels but subsequently lowered daytime glucose levels in normal and diabetic db/db mice. The glucose-elevating and -lowering effects of orexin A were suppressed by adrenergic antagonists and hepatic parasympathectomy, respectively. Moreover, the expression levels of hepatic gluconeogenic genes, including Pepck, were increased and decreased by orexin A at nanomolar and femtomolar doses, respectively. These results indicate that orexin can bidirectionally regulate hepatic gluconeogenesis via control of autonomic balance, leading to generation of the daily blood glucose oscillation. Furthermore, during aging, orexin deficiency enhanced endoplasmic reticulum (ER) stress in the liver and caused impairment of hepatic insulin signaling and abnormal gluconeogenic activity in pyruvate tolerance test. Collectively, the daily glucose rhythm under control of orexin appears to be important for maintaining ER homeostasis, thereby preventing insulin resistance in the liver.Maintaining glucose and energy homeostasis throughout the day is essential for survival. Therefore, different metabolic functions are timely activated according to the circadian rhythm. Recently, it has also become clear that fine tuning of daily metabolic rhythms is crucial for preventing metabolic abnormalities. For instance, chronic disruption of circadian rhythm in humans, as seen in shift workers, increases the risk of obesity and type 2 diabetes (1,2), and circadian rhythms of glucose regulation are impaired in diabetic animals and patients with diabetes (3).Circadian rhythms of peripheral tissues, including liver, are entrained to the central biological clock located in the suprachiasmatic nuclei (SCN) via autonomic and hormonal pathways (4). The liver plays a pivotal role in maintaining optimal glucose levels via hepatic glucose production (HGP) and glucose uptake. The daily rhythm of HGP is regulated by the autonomic nervous system under SCN control, leading to generation of a daily rhythm in basal blood glucose levels independently of the feeding rhythm (5). The central clock is also crucial for preventing metabolic abnormalities

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“…The differences in the performance of both types of tissue could be related to the different functions in which glucosensing systems might be involved in these tissues, such as the control of food intake and counter-regulation of hypoglycemia in central areas, and homeostatic control of glucose in liver (Polakof et al, 2011). There are almost no studies regarding the circadian regulation of liver metabolism in fish, but in mammals the metabolism of the liver is in part under the control of circadian regulation, and several metabolic genes follow a circadian expression in this tissue, such as GK, phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase) or GSase (Desvergne et al, 2006;Cailotto et al, 2008). The daily variations in liver glucosensing capacity, possibly modulated by melatonin, could be associated with the circadian regulation of metabolism within this tissue.…”

Section: Discussionmentioning

confidence: 99%

Glucosensing capacity in liver of rainbow trout displays day-night variations possibly related to melatonin action

Conde-Sieira

López‐Patiño

Míguez

et al. 2012

Journal of Experimental Biology

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SUMMARYTo assess whether the glucosensing capacity in peripheral (liver and Brockmann bodies) and central (hypothalamus and hindbrain) locations of rainbow trout displays day-night variations in its response to changes in circulating glucose levels, we evaluated the response of parameters related to glucosensing [glucose, glycogen and glucose 6-phosphate levels, activities of glucokinase (GK), glycogen synthetase (GSase) and pyruvate kinase (PK), and mRNA abundance of GK, glucose transporter 2 (GLUT2), and K ATP channel subunits Kir6.x-like and sulfonylurea receptor (SUR)-like] in fish subjected to hyperglycemic treatment under night or day conditions. No day-night significant variations were noticed in the glucosensing capacity of the hypothalamus, hindbrain and Brockmann bodies. In contrast, a clear differential response was noticed in the liver, where glucose levels, GK activity (and mRNA levels) and GSase activity displayed increased values during the day in hyperglycemic fish compared with controls, and lower (GK mRNA levels) or non-existent (glucose, GK and GSase activities, and Kir6.x-like mRNA levels) values during the night. A similar decrease in parameters related to glucosensing in the liver was observed when fish under day conditions were treated with melatonin, suggesting a modulatory role of melatonin in day-night changes of the glucosensing response in the same tissue.

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Daily Rhythms in Metabolic Liver Enzymes and Plasma Glucose Require a Balance in the Autonomic Output to the Liver

Cited by 87 publications

References 41 publications

The autonomic nervous system regulates postprandial hepatic lipid metabolism

The autonomic nervous system regulates postprandial hepatic lipid metabolism

Hypothalamic Orexin Prevents Hepatic Insulin Resistance via Daily Bidirectional Regulation of Autonomic Nervous System in Mice

Glucosensing capacity in liver of rainbow trout displays day-night variations possibly related to melatonin action

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