Increased energy expenditure after intravenous administration of amino acids.

Nutrient-induced thermogenesis (NIT) after parenteral administration of amino acids (AAs) was investigated in rats and compared with result obtained with intragastric administration. Resting energy expenditure was measured with a new type of open-circuit indirect calorimeter. The NIT increased shortly after parenteral AAs administration and reached a steady state in 30 minutes. The change in resting energy expenditure (the increment of resting energy expenditure over preinfusion baseline values) showed a significant relationship not only with the amount of infused AAs but also with the AA concentration in the portal vein. Furthermore, the increase in plasma AA concentrations in the portal vein was proportional to the amount of the particular AA infused. This relationship held true over the entire range tested. NIT with parenteral infusion (11% to 12%) was lower than that with intragastric infusion (20% to 23%). Plasma insulin, corticosterone, and glucagon levels increased after both parenteral and intragastric AAs administration, but the two methods did not show any significant differences in hormonal changes. The plasma aminogram of the portal vein after intragastric infusion was compared with that after parenteral infusion. Total plasma AA concentration and the levels of glutamine, lysine, arginine, glutamate, aspartate, and histidine were lower but the level of isoleucine was higher after intragastric infusion. On the basis of these results, it is believed that parenteral administration of AAs can induce thermogenesis, which may be regulated by the intraportal AA concentration. Considering the remarkable decrease in glutamine in the portal vein after intragastric infusion, the cost of intestinal metabolism may predominantly contribute to the NIT resulting from intragastric infusion.     

支链氨基酸对创伤后代谢影响的研究

目的:观察应用支链氨基酸对手术创伤病人机体代谢的影响. 方法:采用前瞻、随机、单盲、平行、对照、多中心试验设计,选择行腹部外科手术后成年病人120例,随机分为两组:对照组(n=60)应用10.4% 18种复方氨基酸注射液,研究组(n=60)应用10.3%支链氨基酸注射液.采用全营养混合液方式行周围或中心静脉输注,等氮等热量.从术后第2天开始,应用6天.在手术前1天和术后第7天,对所有病人收集空腹血标本检测,同时进行24 h尿液收集作氮平衡分析. 结果:研究组与对照组之间在研究前、后累积氮平衡无明显差异,但在营养液输注第5天,研究组氮平衡显著高于对照组(P<0.01).两组之间研究前、后血清总蛋白、前清蛋白、纤维连接蛋白、转铁蛋白和体重变化无显著差异.两组研究前、后血清清蛋白浓度均降低,但对照组下降更为明显(P<0.05).研究组应用氨基酸后,缬氨酸浓度升高明显,与对照组相比差异显著(P<0.05).缬氨酸、丙氨酸和支链氨基酸浓度较输注前明显升高(P<0.05). 结论:对手术创伤应激病人的肠外营养支持中,应用含较高支链氨基酸的营养液较平衡氨基酸注射液可能更为有效.     

Extracellular hypothalamic serotonin and plasma amino acids in response to sequential carbohydrate and protein meals

In previous studies, we showed that carbohydrate and protein ingestion, respectively, increased and decreased hypothalamic extracellular serotonin and the plasma ratio tryptophan over its competitor amino acids (Trp/LNAAs), reflecting serotonin synthesis. Serotonin levels returned towards baseline 2 h after either meal while the ratio remained altered. The question addressed is the ability of serotonin to respond expectedly to a second meal of the alternate nutrient. Rats were fed with sequential meals of either carbohydrates first and then casein 2 h later or in reverse order. Hypothalamic serotonin was measured using microdialysis. Permanent blood sampling allowed to track in parallel plasma amino acids. A carbohydrate meal increased hypothalamic serotonin, so did a subsequent casein meal. Conversely, following a casein meal that reduced serotonin, a carbohydrate meal also decreased it. The plasma ratio Trp/LNAAs was enhanced by a carbohydrate meal and remained high for 2h. A subsequent casein meal reversed this change but the ratio remained higher than basal values. A first casein meal reduced the ratio that was not increased again by a subsequent carbohydrate meal. It is obvious that ingestion of specific nutrients induce long-lasting metabolic and neurochemical variations that prevent subsequent changes to occur. The lack of expected changes to a second meal addresses again the hypothesis of alternate appetites for carbohydrates and proteins driven by serotonin changes.     

Effects of intravenous amino acids on anesthesia-induced hypothermia in ovariectomized rats

A decrease in core temperature during general anesthesia is attenuated by infusion of an intravenous amino acid mixture. The purpose of the present study was to investigate the influence of physical and endocrine changes caused by ovariectomy on the inhibitory effect of amino acid infusion on anesthesia-induced hypothermia. Sprague-Dawley female rats were divided into a sham-operated (Sham) group and an ovariectomized (OVX) group. Saline solution or an amino acid mixture solution was infused for 180 min during sevoflurane anesthesia, and the rectal temperature was measured (4 groups). Intraperitoneal white adipose tissue mass, bilateral gastrocnemius weight and plasma insulin levels were measured. In the Sham rats, no inhibitory effect of the amino acid mixture on anesthesia-induced hypothermia was found, while in the OVX rats, hypothermia was significantly decreased. The intraperitoneal fat weight/body weight ratio was significantly higher in the OVX rats than in the Sham rats, but the gastrocnemius weight/body weight ratio was not significantly different. After amino acid infusion, the plasma insulin level was significantly higher in the OVX rats than in the Sham rats. In conclusion, our findings suggest that, in rats, ovarian function or female hormone affects protein turnover mediated by increase in insulin secretion and, thus, decreases the inhibitory effect of an infusion of amino acid mixture on anesthesia-induced hypothermia.     

Gallbladder contraction after administration of intravenous amino acids and long-chain triacylglycerols in humans.

We examined the possible physiologic effects of intravenous (IV) amino acids (AAs) and long-chain triacylglycerols (LCTs) on gallbladder (GB) motility and release of cholecystokinin (CCK) on humans. GB contraction was studied in normal volunteers after administration of a fatty meal and IV infusion of AA and LCT. The GB contraction volume was calculated with ultrasound. Cholecystokinin-8 (CCK-8) and cholecystokinin-33/39 (CCK-33/39) were measured by radio-immunoassay. Administration of a fatty meal resulted in GB contraction by 60% of its basal volume and was accompanied by an increase in the serum levels of both CCK-8 and CCK-33/39. Administration of IV AA and LCT resulted in GB contraction by 17 and 37%, respectively, of its basal volume. The latter contractions were accompanied by increased levels of CCK-8 only. We conclude that IV administration of AA and LCT can result in human GB contraction and induce the release of only CCK-8. Continuous IV administration of AA and LCT for greater than 2h causes exhaustion of CCK-8 release, so that the GB returns to its initial volume.     

Effects of branched-chain amino acid supplementation on plasma concentrations of free amino acids, insulin, and energy substrates in young men

The present study was conducted to examine alterations in the concentrations of plasma free amino acids, glucose, insulin, free fatty acids (FFAs), and urea nitrogen induced by branched-chain amino acid (BCAA) supplementation in young men. Overnight-fasted subjects ingested drinks containing 1 or 5 g of a BCAA mixture (weight ratio of 1 : 2.3 : 1.2 for isoleucine : leucine : valine), and blood was intermittently collected for 3 h after ingestion. Ingestion of the BCAA mixture resulted in significant increases in the plasma concentrations of individual BCAAs, corresponding to the amounts of amino acids ingested. On the other hand, plasma concentrations of methionine and aromatic amino acids tended to decrease in the trial with 5 g BCAAs, suggesting that BCAA ingestion affects the metabolism of these amino acids. The ingestion of BCAAs temporarily increased plasma insulin levels and affected plasma concentrations of FFAs, but had almost no effect on glucose or urea nitrogen.     

Peri-operative amino acid administration and the metabolic response to surgery

General anaesthesia causes hypothermia due to decreased metabolic rate and impaired thermoregulation. Many warming devices are in use to prevent heat loss, but little attention has been paid to stimulating the body's own heat generation. All nutrients raise energy expenditure, and the highest thermic effect is ascribed to amino acids and proteins, 30-40 % in the awake state. Amino acids infused during general anaesthesia exert a thermic effect that is enhanced compared with that in the awake state. At awakening from anaesthesia, post-operative hypothermia may be prevented without shivering. The tissues involved and the mechanisms by which nutrients stimulate heat production are still not completely understood. However, these findings support the existence of an inhibitory action normally exerted by central thermosensors, in order to maintain oxidative metabolism within certain limits, to prevent hyperthermia. During anaesthesia central thermosensors are silenced and, hence, amino acid thermogenesis is exaggerated. The amino acid-induced heat generation during anaesthesia predominantly occurs in extra-splanchnic tissues, most probably in skeletal muscle. It may reflect an increased protein turnover, as both protein breakdown and synthesis are energy-consuming processes known to generate heat. Possibly, amino acid infusion provides substrates, otherwise mobilized from the body's own tissues, needed for wound healing and immunological function. However, other cellular mechanisms may also contribute to this non-shivering thermogenesis.     

Effects of intravenous infusion of a ten percent soybean emulsion on hormones, amino acids and other substrates in blood

Acute responses in hormone and substrate concentrations to intravenous administration of a fat emulsion were studied in metabolically normal subjects. Eight subjects were infused with either a fat emulsion or an aqueous solution of glycerol for 3 h. Serum triglycerides (TG), free fatty acids (FFA), glucose, glycerol, 3-hydroxybutyrate (3-OH butyrate), insulin, thyroid hormones, plasma glucagon, norepinephrine, and amino acids were measured. The infusion of a fat emulsion induced a 30% increase in glucose and a 22% decrease in alanine together with significant elevations of TG (> 10 mM) and FFA (> 1 mM). A small increase in insulin (4 microU/ml) and a reduction in glucagon (40 pg/ml) were observed. Eight-fold increases in glycerol occurred with both the fat emulsion and glycerol infusions. The administration of a fat emulsion resulted in a 4-fold increase in 3-OH butyrate, whereas glycerol infusion reduced its level by 50%. Glycerol infusion produced no measurable effects on the substrates other than glycerol or 3-OH butyrate. No significant changes were observed in thyroid hormones or norepinephrine after either solution was given. The data suggest that acute elevation of FFA by means of intravenous fat emulsions leads to preferential oxidation of FFA and stimulates hepatic ketogenesis with resulting glucose conservation as well as inhibition of alanine production without many alterations in hormonal concentrations.     

Enhanced rate of ethanol elimination from blood after intravenous administration of amino acids compared with equicaloric glucose

AIMS: To investigate the effect of an amino acid mixture given intravenously (i.v.) on the rate of ethanol elimination from blood compared with equicaloric glucose and Ringer's acetate as control treatments. METHODS: In a randomized cross-over study, six healthy men (mean age 23 years) fasted overnight before receiving either Ringer's acetate, glucose or the amino acid mixture (Vamin 18 g N/l) by constant rate i.v. infusion over 4.5 h. Ethanol (0.4 g/kg) was given by an i.v. infusion lasting 60 min during the time each of the treatments was administered. At various times post-infusion, blood samples were taken for determination of ethanol by headspace gas chromatography. Blood glucose and heart rate were monitored at regular intervals. Concentration-time profiles of ethanol were plotted for each subject and the rate of ethanol disappearance from blood as well as other pharmacokinetic parameters were compared by repeated measures analysis of variance. RESULTS: The rate of ethanol elimination from blood was increased significantly (P < 0.001) after treatment with amino acids (mean +/- SD, 0.174 +/- 0.011 g/l/h) compared with equicaloric glucose (0.121 +/- 0.016 g/l/h) or Ringer's acetate (0.110 +/- 0.013 g/l/h). Heart rate was also slightly higher during infusion of the amino acid mixture (P < 0.05). CONCLUSIONS: When the rate of ethanol elimination from blood is relatively slow, such as after an overnight fast, it can be increased by approximately 60% after treatment with i.v. amino acids. The efficacy of amino acid treatment was not related to the supply of calories because glucose was no more effective than Ringer's acetate. We suggest that amino acids might increase hepatic oxygen consumption, resulting in a more effective conversion of NADH to NAD+ in mitochondria. An important feature of the experimental design was ensuring hepatic availability of amino acids during much of the time that ethanol was being metabolized.     

Amino acid levels in plasma and muscle of rats after intravenous administration of different amino acid infusions

Studies were conducted on the participation of specific amino acids in the alterations of their levels in plasma and muscle of rats after short term intravenous infusion. Sufficient amounts of amino acids and glucose were used as a basal solution, and the levels in plasma and muscle were determined 30 min after the end of infusion. When an infusion solution devoid of one of the essential amino acids from the basal solution, -Leu, -Ile, -Lys or -Thr, was administered, the plasma and muscle levels of the deleted amino acids decreased in different degrees. With infusion of the deficient solutions except for the -Leu, no significant changes were observed in amino acids other than those deleted, although occasional changes were noted. On the other hand, the infusion of the -Leu resulted in significant increase of isoleucine and valine levels, and a moderate increase of many other amino acids both in plasma and in muscle. In contrast, when leucine was administered singly in an amount equivalent to that in the basal solution, isoleucine and valine decreased significantly. Most of the other amino acids also decreased markedly after the infusion of leucine alone. These results suggest that, in intravenous infusion, leucine plays a specific role on amino acid levels in plasma and muscle of rats.     

Metabolic effects of four intravenous nutritional regimens in patients undergoing elective surgery II.--Muscle amino acids and energy-rich phosphates

Muscle amino acids and energy-rich phosphates have been determined in 28 patients before and after resection of a carcinoma of colon or rectum. Before operation the patients received a synthetic diet (Vivasorb for four days and postoperatively four different intravenous regimens with different amounts and proportions of amino acids were given for six days, the energy intake being the same for all groups. When compared with age-matched healthy controls the patients showed only slight increases in phenylalanine and isoleucine concentration in muscle and plasma with elevated plasma glutamate during the four days prior to the operation. Vivasorb treatment increased the concentration of alanine, glycine and methionine in both muscle and plasma while increases of threonine and histidine were seen only in muscle. Decreased concentrations of valine were found in muscle and plasma, while lysine and leucine decreased only in plasma. As an effect of operation, but independent of the nutritional regimen, muscle asparagine increased and muscle glutamine and glutamate decreased in all groups. The unique pattern of amino acid changes in postoperative trauma was confirmed in the present investigation but few differences in amino acid concentrations could be related to the various nutritional intakes. Alterations in the individual amino acid concentrations were not influenced by the intake of amino acids and seemed to have little relationship to the composition of any solution infused. Prior to operation there were low levels of ATP in muscle possibly due to immobilisation and chronic semistarvation but no changes in the energy rich phosphates could be attributed to trauma or nutrition. The content of muscle glycogen increased as a result of the Vivasorb supply indicating that the preoperative carbohydrate administration promotes muscle glycogen synthesis and postoperatively muscle glycogen was reduced significantly indicating enhanced glycogenolysis in the postoperative state. This finding emphasizes the importance of providing the patients with ample amount of glucose before and after surgery.     

晚期早产儿早期静脉补充氨基酸治疗的临床研究

【目的】 评价晚期早产儿(34 ~36⁺⁶周)中,在生后2 h内给予静脉补充氨基酸的效果和安全性。 【方法】 将115例患儿随机分为两组,治疗组在生后2 h内给予静脉输注氨基酸[2.4 g/(kg·d)],对照组则在生后第1天仅给予输注葡萄糖治疗,在第3天逐渐增加到氨基酸2.4 g/(kg·d)。并动态测定患儿的血气、血糖、BUN及氮平衡情况。 【结果】 治疗组患儿的BE和HCO^{₃在生后的第2、4天均低于对照组(P<0.05或0.01)。生后第2天血糖监测显示对照组较治疗组偏高(P<0.05)。治疗组生后第2、4天的血尿素氮水平明显高于对照组(P<0.01)。生后第2天,治疗组的氮平衡明显高于对照组(P<0.05),并且对照组呈负氮平衡。 【结论】 对晚期早产儿早期补充高剂量氨基酸是安全的,使机体处于合成代谢状态,为生长发育所必需。}     

Effect of dietary amino acids on behavior and serum levels of amino acids in stress loaded rats

Interrelationships between behavior and concentrations of serum amino acids in stressed rats with immobilization and water immersion were investigated. Rats were subjected to 7 h of immobilization with water-immersion stress (IWS) in each sequential day, and serum amino acids were then determined. On the first day, serum taurine, threonine, valine, leucine, isoleucine, phenylalanine, lysine, and histidine (increased-type of amino acids) were significantly increased, but alanine (decreased-type) was significantly decreased. On days 3 and 7, the increase was retained, except for threonine, histidine, and lysine. Spontaneous activities (locomotion, rearing behavior, hole-poking) under loading water-immersion stress were significantly decreased, but a supplementation of branched-chain amino acids (BCAA) led to recovery. We suggest that pretreatment with some kind of increased type of amino acid, such as BCAA, might effectively prevent decline in spontaneous activities evoked by water-immersion stress.