Hepatic Vagotomy Research Articles

Altered hepatic metabolic response to carbohydrate loads in rats with hepatic branch vagotomy or cholinergic blockade

Hepatic pyruvate, lactate and glycogen concentrations were measured 40 min after gavage of 5 ml 35% fructose or glucose to rats with sham surgery or section of the hepatic branch of the vagus nerve. Other animals were treated with saline or the peripheral anticholinergic drug, atropine methyl nitrate, prior to gavage of fructose. The increase in pyruvate concentration produced by the carbohydrate loads was attenuated by both hepatic vagotomy and cholinergic blockade. The increase in lactate concentration after a fructose load was attenuated by hepatic branch vagotomy but not atropine injection. The increase in glycogen deposition after a fructose load was attenuated by atropine injection but not hepatic branch vagotomy. These results suggest that the hepatic metabolic response to fructose and glucose loads in rats depends on a functional parasympathetic nervous system.

Hepatic vagotomy effects on metabolic challenges during parenteral nutrition in rats.

During parenteral nutrition (PN) glucoprivic-induced feeding appeared to be neutralized by the oxidation of infused fatty acids. With the use of a latin-square design, the feeding response to 2-deoxy-D-glucose (2-DG) and/or 2-mercaptoacetate (MA) was evaluated in male Sprague-Dawley rats with hepatic branch vagotomy (HV) or sham operations (SO). Rats received continuous infusions of 0.9% saline or PN providing 100% of daily caloric needs (PN-100) for four consecutive days. During PN-100, food intake was stimulated by 2-DG in HV rats and when fatty acid oxidation was simultaneously inhibited by MA. 2-DG-induced hyperglycemia was apparent under all conditions. Lipoprivic-induced feeding and increased plasma free fatty acid concentrations were absent in HV rats, whether MA was administered alone or with 2-DG. The feeding response to glucoprivic challenges is influenced by the relative availability of alternate energy sources. The lack of feeding response to 2-DG during PN-100 is mediated by vagal input of hepatic fatty acid oxidation status.

Influence of age and hepatic branch vagotomy on the night/day distribution of food intake in rats

The aim of the present study was to investigate the influence of age and hepatic branch vagotomy on the night/day distribution of food intake in male rats. Food intake of young (age: 2 months) and aged (age: 13.5 months) hepatic branch vagotomized (HBV) and sham-vagotomized (SV) rats was measured at intervals of 6 h during the 12 h dark and the 12 h light phase. The results show that in rats the night/day ratio of food intake decreases with age and is not affected by hepatic branch vagotomy. However, the time-course of spontaneous diurnal food intake was influenced by hepatic branch vagotomy. The change in the night/day distribution of food intake might be due to age-related changes in the nucleus suprachiasmaticus of the hypothalamus.

Hepatic glucose signals vagally modulate the cyclicity of gastric motility in rats.

The cyclicity and intensity of gastric motility were examined following glucose injection into the portal vein with an intragastric balloon in anesthetized rats. Enhanced gastric motility caused by insulin administration was influenced by 4 mM glucose (25 microliters) injected into the portal vein; glucose provoked a shift in the cyclicity power spectrum without any change in intensity. The peak power spectrum shifted from 4.0-5.0 cpm to 2.0-3.0 cpm. Hepatic branch vagotomy abolished the response. The results suggest that glucose signals in the hepatic vagal branch modulate the cyclicity of gastric motility.

Modulation of insulin secretion by hepatic vagotomy in cirrhotic rats

There is evidence that glucose sensors and arginine sensors are present in the hepato-portal system and exert a reflex regulation of the pancreatic neuroendocrine system in normal rats. To investigate the function of these sensor systems in liver cirrhosis, we examined the effect of hepatic vagotomy on plasma glucose and insulin concentrations after intraperitoneal (IP) injection of glucose or l-arginine in carbon tetrachloride (CCl 4)-induced cirrhotic rats. After IP glucose injection, hepatic vagotomy decreased plasma insulin with elevation of plasma glucose in control rats; however, in cirrhotic rats, this procedure did not affect either plasma glucose or insulin concentrations. After IP arginine injection, hepatic vagotomy increased plasma insulin and reduced plasma glucose in control rats, although in cirrhotic rats, this procedure did not affect plasma glucose but did increase plasma insulin concentrations. These results suggest that function of the glucose sensor in CCl 4-induced cirrhotic rats is disturbed, although that of the arginine sensor is retained.

Hepatic vagal amino acid sensors modulate amino acid induced insulin and glucagon secretion in the rat

To clarify the physiological role of vagal amino acid sensors in the liver, the effect of hepatic vagotomy and/or celiac vagotomy (sectioning of the hepatic branch and/or celiac branches of the vagus nerve) on the secretion of insulin and glucagon after intraperitoneal injection of neutral ( l-alanine, l-leucine, and l-phenylalanine), acidic ( l-glutamate), or nonmetabolized (cycloleucine) acids, was examined in rats. Hepatic vagotomy enhanced both plasma glucose and glucagon concentrations after intraperitoneal injection of alanine more than those in sham-vagotomized (control) rats, while after intraperitoneal injection of leucine, hepatic vagotomy decreased plasma glucose concentrations and enhanced plasma insulin concentrations more than in control animals. These effects, following both alanine and leucine administration, were blocked by celiac vagotomy. Glutamate, phenylalanine, and cycloleucine stimulation in hepatic-vagotomized rats caused no significant differences in plasma glucose, insulin, or glucagon levels as compared to those in sham-vagotomized rats. Celiac vagotomy alone did not affect plasma glucose, insulin, or glucagon concentrations after stimulation by these five amino acids. The physiological role of alanine and leucine sensors may be to prevent amino acid-induced exaggerated pancreatic hormone secretion and to maintain blood glucose homeostasis, while glutamate, phenylalanine, and cycloleucine have no effect on this pancreatic neuroendocrine system.

Effects of hepatic vagotomy on suppression of water intake induced by hepatic portal infusion of water in water-deprived rats

We investigated the effects of hepatic vagotomy on the suppression of water intake induced by hepatic portal infusion of water by 24-h water-deprived rats. In sham-operated rats, water intake of the portal infusion group was significantly less than that of the jugular infusion group during and after the infusion of deionized water for 3.5 h at a rate of 52 μl/min. This result reconfirmed our previous findings. On the other hand, in hepatic-vagotomized rats, the suppression during the portal infusion of water was not observed, but the suppression after portal infusion was observed. It is concluded that the suppression, at least during the portal infusion of water, was mediated by hepatoportal osmo-receptive (or sodium-receptive) afferent signals contained in the hepatic branch of the vagus nerve.

Hepatic vagotomy does not disrupt the normal satiation of NaCl appetite

The necessity of the hepatic branch of the vagus nerve for the normal satiation of NaCl intake under the condition of sodium depletion was tested. Sham- or hepatic-vagotomized male, Long-Evans rats were sodium depleted by injection with Lasix (furosemide, 10 mg) and were maintained overnight on sodium-deficient diet and water. The intake of 0.3 M NaCl during a 2-h salt appetite test was not significantly different between the sham- and hepatic-vagotomized groups. In a second group of sham- or hepatic-vagotomized rats, a load of 7.5 ml of 0.5 M NaCl was given by gavage at 15 or 90 min prior to a 1-h NaCl appetite test. The preload decreased NaCl intake equivalently in both groups. Gastric emptying of a preload of NaCl at 15 and 90 min was also the same for sham- and hepatic-vagotomized rats. Thus, the hepatic branch of the vagus nerve is not necessary for the normal short-term satiation of NaCl intake under the condition of acute sodium depletion produced by furosemide.

Hepatic vagotomy does not alter plasma insulin response to a low dose injection of glucose

It was been reported that insulin concentration is altered by a hepatic vagotomy following intraperitoneal glucose injection (0.3 g/kg) resulting in supraphysiological blood glucose concentrations. On the other hand, neural activity of the hepatic vagus nerve has been shown to be substantially reduced by lower doses (0.05 g/kg intraportal; 0.1 g/kg intravenous). The present study was conducted in order to examine the role of the hepatic vagus nerve in insulin response after intraperitoneal injections of 0.1 and 0.3 g/kg of glucose. Measurements were made 5 days after section of this branch. In a first experiment, arterial glucose and insulin concentrations were not affected by the hepatic vagotomy following injections of either 0.1 or 0.3 g/kg of glucose. The same finding was also found in a second experiment in which portal glucose and insulin levels were measured after injection of 0.1 g/kg of glucose. These results suggest that large changes in neural activity are needed for the hepatic vagus nerve to influence the insulin response.

Influence of anterior subdiaphragmatic vagotomy and TPN on rat feeding behavior

Total parenteral nutrition (TPN) inhibits food intake and feeding behavior. Whether caloric sensory function of the liver contributes to this food intake and feeding behavior regulation via vagal-afferent innervation was tested after performing anterior hepatic vagotomy or sham operation in rats infused with a TPN solution providing 100% of daily energy needs, given continuously for 4 days. Food intake, meal number, size, duration, meal and intermeal sniffs, and eating activity were measured using an automated computerized rat eater meter (ACREM). TPN infusion resulted in a significant decrease of food intake and feeding indexes in both groups. The vagotomized rats showed a significantly higher food consumption, achieved by greater meal frequency, larger meal size, and longer meal duration. Thus, vagotomized rats consumed more than their controls by eating larger meals more often and longer duration. Data suggest that anterior hepatic vagotomy interrupts hepatic caloric sensory feedback loop, diminishing inhibitory vagal effects on food intake with TPN, leading to an overall increase in food intake.

Role of vagus nerve in increased DNA synthesis after hypothalamic ventromedial lesions in rat liver.

We recently reported that ventromedial hypothalamic (VMH) lesions produced an increase in DNA content in rat liver. In the present study, we examined the mechanism of increased hepatic DNA content produced by VMH lesions. Hepatic DNA content began to increase 3 days after VMH lesioning and continued to increase until 7 days after the lesioning. Hepatic DNA synthesis increased and reached maximum 3 days after the lesioning and then decreased to the initial level 7 days after lesioning. The increased DNA content and synthesis after VMH lesioning were completely inhibited by vagotomy (hepatic vagotomy or bilateral subdiaphragmatic vagotomy) and largely inhibited by the administration of atropine but not by administration of anti-insulin antibody. These results suggest that vagus firing produced by VMH lesions stimulates DNA synthesis in rat liver mainly through cholinergic receptor mechanisms.

Effects of hepatic vagotomy on suppression of water intake during portal infusion of water by water deprived rats

Effects of hepatic vagotomy on suppression of water intake during portal infusion of water by water deprived rats

Role of the efferent and afferent vagus nerve in the development of ventromedial hypothalamic (VMH) obesity

Hyperactivity of the vagus nerve and hypoactivity of the sympathetic nerves after VMH lesions both cooperatively contribute to the development of VMH obesity, mainly through hyperinsulinemia. Recently it has turned out that we should discriminate the role of the efferent vagus from that of the afferent vagus in the pancreatic hormone secretion. The hepatic branch is the main pathway of afferent fibers in the vagus, while the celiac (pancreatic) branch is the main pathway of efferent fibers. We investigated the role of the afferent and efferent vagus on the development of VMH obesity using the sectioning of the hepatic and celiac branch. Celiac vagotomy decreased insulin secretion and food intake, while hepatic vagotomy did not change them. The results suggested that the efferent vagus plays the main role in the development of VMH obesity, while the role of afferent vagus seems less apparent.

2,5-anhydro-D-mannitol acts in liver to initiate feeding

We determined the site at which the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) acts to increase food intake in rats. Rats began eating sooner and ate more food during hepatic portal than during jugular infusions of 2,5-AM (50, 100, or 150 mg/h). After rats were intubated with 2,5-[14C]AM (1.15 microCi in 200 mg/kg), significant quantities of radioactivity were found in liver but not in brain. Hepatic vagotomy prevented the eating response to 200 mg/kg 2,5-AM without altering the effect of the analogue on plasma fuels. These results indicate that low doses of 2,5-AM act in the liver to increase food intake and suggest that the signal for feeding generated in the liver is transmitted to the brain through the hepatic vagus nerve. Taken together, this work provides the strongest evidence to date that a signal initiating feeding behavior originates in the liver.

Effect of hepatic vagotomy on hormonal response to exercise in gluconeogenesis-inhibited rats

The liver, through the afferent pathway of the hepatic vagus nerve, has been reported to influence the hormonal response to exercise in adrenodemedullated rats. The present investigation was designed to evaluate the role played by gluconeogenesis in this hepatic influence. To this end, we studied the effects of a selective hepatic vagotomy on the hormonal response to a 30-min treadmill run (26 m/min, 0% grade) in adrenodemedullated rats injected with 3-mercaptopicolinic acid, a gluconeogenic inhibitor. Hepatic vagotomy was associated with small but significant higher (P less than 0.05) elevations of peripheral blood glucose levels at rest and after exercise. No significant differences were observed between hepatic-vagotomized and sham-operated rats in either resting or exercising levels of liver glycogen, portal glucose, portal and peripheral insulin and glucagon, and peripheral epinephrine and norepinephrine. All hormonal responses, with the exception of epinephrine, were either decreased or increased similarly in the two experimental conditions after exercise. These data indicate that contrary to what has been reported in rats with an intact capacity for gluconeogenesis, hepatic-vagotomized and sham-operated rats with an inhibited gluconeogenesis had similar hormonal responses to exercise. It is concluded that gluconeogenesis plays a role in the afferent neural influence exerted by the liver via the hepatic vagus nerve in the regulation of hormonal response to exercise.

Effects of selective hepatic vagotomy on running endurance in rats

The liver, through the afferent ways of the vagus hepatic nerve, may influence metabolic adaptations during exercise. This study assesses the functional significance of this hepatic innervation by determining the effect of a selective hepatic vagotomy (HV) on running endurance time during submaximal activity in rats subjected to an overnight 50% food restriction. The time to exhaustion was similar for the groups of HV and sham-operated (SHM) rats [66 +/- 15 vs. 64 +/- 21 (SD) min]. The HV group was associated with higher resting levels (P less than 0.05) of hepatic glycogen and plasma glucose. No significant differences were observed between HV and SHM rats at rest and after exercise for muscle glycogen, free fatty acids, insulin, glucagon, and lactate concentrations. These data indicate that if hepatic glucoreceptors do exist and contribute to the metabolic regulation of exercise, their functional significance is secondary to more important regulatory mechanisms.

Modulation of Arginine-Induced Insulin and Glucagon Secretion by the Hepatic Vagus Nerve in the Rat: Effects of Celiac Vagotomy and Administration of Atropine

We hypothesized the existence of vagal arginine sensors in the liver which modulate arginine-induced pancreatic hormone secretion. The present study was carried out to examine the efferent pathways and receptor mechanisms from arginine sensors using selective vagotomies and autonomic drugs on the secretion of insulin and glucagon after ip injection of L-arginine (1 g/kg BW) in rats in an unanesthetized and unrestrained state. Hepatic vagotomy (sectioning of the hepatic branch of the vagus nerve) enhanced both plasma insulin and glucagon concentrations after ip arginine more than those in sham-vagotomized (control) rats. The effect of hepatic vagotomy was blocked by adding celiac vagotomy (sectioning of the celiac branches of the vagus nerve) or by previous administration of atropine methyl nitrate (10 mg/kg BW), but not by phentolamine (1 mg/kg BW) or propranolol (2 mg/kg BW). Celiac vagotomy alone did not affect the plasma insulin concentration; however, it reduced the plasma glucagon concentration after ip arginine compared to that in sham-vagotomized rats. Administration of atropine alone did not affect plasma insulin or glucagon concentrations after ip arginine. These results suggest that celiac branches of the vagus nerve act as efferent pathways to the pancreas through a muscarinic receptor mechanism in the hepatic arginine sensor-mediated pancreatic neuroendocrine system. The physiological role of these hepatic sensors may be to prevent arginine-induced exaggerated pancreatic hormone secretion and maintain blood glucose homeostasis.

Feeding pattern of liver-transplanted rats

It has been proposed that the liver is involved in the control of food intake (FI). Various studies utilizing hepatic vagotomy have cast doubt on the role of hepatic metabolic receptors. Feeding patterns of male adult Lewis rats were continuously recorded in one group of animals after orthotopic liver transplantation (T), without reestablishing arterial flow. Rats of a second group were dearterialized (D) and had their livers freed from the hepatic pedicle, while rats of a third group were laparotomized (L) and served as sham-operated controls. Meal pattern analyses and body weight (BW) changes were followed after surgery. When T rats began to recover BW, a fourth nonoperated control group (C) was added with BW paired to the T group. From days 15 to 25 the T rats gained significantly less BW than C rats and their 24-hour FI was reduced: daytime FI was augmented while nighttime FI was decreased. Meal number was unchanged. Daytime meal size was increased while nighttime meal size was diminished. Between days 50–60, the BW gain of the T group was nearly identical to that of D or L rats from days 15–25. Data from these two periods were compared. The 24-hour FI was identical, nighttime FI remained significantly lower in T rats. Because of variation in BW recovery of the T rats an additional comparison was made between the T rats after they recovered their BW following surgery, and the D and L rats (days 15–25). All feeding pattern parameters were identical in T, D and L rats. Liver transplantation was followed only by small long-lasting changes. Hypotheses about the role of liver innervation in feeding behavior focus on direct signals from metabolic receptors to the brain. Possible disturbances in liver glycogen depletion or repletion mechanisms and inbiliary excretion also have to be taken into account.

Hepatic lipase activity after liver denervation in hypothyroid rats

Hepatic hilar denervation, hepatic vagotomy or sham operation were performed in hypothyroid rats. Activities of hepatic lipase were measured nine days after surgery. Sham operation in itself was associated with a decrease of hepatic lipase activity by about 40% compared with non-operated animals. Both hilar denervation and hepatic vagotomy were associated with increased hepatic lipase activity (40% and 35%, compared with sham-operated animals). Liver contents of norepinephrine were reduced by about 90% after hilar denervation, whereas hepatic vagotomy did not affect norepinephrine levels. No major changes in lipids and lipoproteins were noted.

The role of the gastric and hepatic vagus in voluntary alcohol intake

The present study investigated a possible role for neural signals sent from the liver and stomach to the brain in the regulation of alcohol intake. Experiment 1 showed that gastric vagotomy (GVX) reduced the intake of 3% alcohol and 6% alcohol, while water intake was increased. This effect was not due to an alteration in pharmacokinetics, although an alteration in taste function could not be ruled out. Angiotensin II reduced the intake of 6% alcohol and stimulated the intake of water similarly in both GVX and sham groups. In Experiment 2 rats were subjected to hepatic vagotomy or sham laparotomy and then offered a choice between an alcohol solution and tap water for 40 min each day. Although hepatic vagotomy (HVX) did not alter the intake of 3% alcohol or water, 6% alcohol intake was significantly reduced. Angiotensin II decreased 6% alcohol intake and increased water intake similarly in both groups. These experiments indicated that interrupting information from the liver and stomach to the brain by selective gastric and hepatic vagotomy can decrease voluntary alcohol intake. Since vagal afferent nerves are thought to participate in the control of food intake, the present findings support the hypothesis that the “food-like” qualities of alcohol, i.e., calories and taste, can contribute to the regulation of alcohol intake.