The influence of abdominal surgical trauma on the exchange of blood-borne amino acids in the human leg

Associated with surgical trauma is an increased release of gluconeogenic substrates from the periphery. The present study was undertaken to investigate the peripheral exchange of blood and plasma amino acids as well as some other gluconeogenic substrates (lactate and glycerol) in connection with abdominal surgery. Measurements of leg blood flow and femoral arterio-venous substrate differences were made before, during and immediately after elective cholecystectomy. Blood and plasma concentrations of most amino acids except alanine decreased during and immediately after surgery. Simultaneously there was an increased release of several of the amino acids as well as lactate and glycerol from the leg. The total release of plasma amino acids from one leg in the immediate postoperative period was about 2.5 times as high as before surgery. The turnover rates of amino acids as well as the changes in turnover rates were comparable whether the calculations were made from plasma or whole blood concentrations. At the end of surgery there was a high peripheral uptake of 3-hydroxybutyrate concomitant with a low release of amino acids.     

Glucose infusion does not suppress increased lipolysis after abdominal surgery

The purpose of this study was to investigate the effect of glucose infusion on lipid metabolism after abdominal surgery. Patients (n = 6) with non-metastasized colorectal carcinoma were investigated on the second day after surgery and healthy volunteers were studied after an overnight fast. The rates of glycerol appearance (R(a) glycerol), i.e., lipolysis rates, were assessed by primed continuous infusion of [1,1,2,3,3,-5H2]glycerol before and after 3 h of glucose infusion (4 mg x kg(-1) x min(-1)). Plasma concentrations of glycerol, free fatty acids, glucose, lactate, insulin, and glucagon were determined. Fasting R(a) glycerol was higher in patients than in volunteers (7.7 +/- 1.8 versus 1.9 +/- 0.3 micromol x kg(-1) x min(-1), P < 0.05). Glucose infusion suppressed the R(a) glycerol in volunteers to 1.0 +/- 0.2 micromol x kg(-1) x min(-1) (P < 0.05), whereas lipolysis was not affected in patients. Plasma concentrations of glycerol and free fatty acids similarly decreased during glucose administration by 50% in both groups (P < 0.05). In contrast to the patients, a significant correlation (r = 0.78, P < 0.05) between the R(a) glycerol and plasma glycerol concentration was observed in normal subjects. The hyperglycemic response to glucose infusion was significantly more pronounced (P < 0.05) in patients (10.7 +/- 0.7 mmol/L) than in volunteers (7.1 +/- 0.4 mmol/L), whereas the plasma insulin increased to the same extent in the two groups (P < 0.001). In conclusion, lipolysis rates are increased after abdominal surgery and glucose administration, most likely due to insulin resistance, and fail to inhibit stimulated whole-body lipolysis.     

Effect of diet on glucose tolerance 36 hours after glycogen-depleting exercise.

In order to estimate the effect of muscle glycogen content on the glycaemic response, glucose tolerance and glucose oxidation were measured in eight healthy male subjects. Each subject followed three different treatments, consisting of either a physical exercise session followed by 36 h of a low-carbohydrate high-fat diet (glycogen depletion treatment); or a physical exercise followed by 36 h of a high carbohydrate diet (glycogen repletion treatment); or a low-carbohydrate high-fat diet alone (diet treatment). After both the glycogen depletion and the diet treatments, the subjects showed a high glycaemic response (443 +/- 57 and 419 +/- 63 mmol.min/l resp.), a high insulinaemic response (7158 +/- 671 and 7643 +/- 913 mU.min/l), and a low rate of glucose oxidation (27.5 +/- 2.4 and 31.0 +/- 5.8 g/3 h respiration). In contrast, after the glycogen repletion treatment, the subjects had a lower glycaemic response (197 +/- 21 mmol.min/l), a lower insulinaemic response (4645 +/- 327 mU.min/l) and a higher glucose oxidation level (47.4 +/- 2.0 g/3h). Fasting free fatty acids (FFA) were positively correlated with glucose area (P less than 0.001) and negatively with glucose oxidation (P less than 0.01). These results show a strong inhibitory effect of the low-carbohydrate high-fat diet on glucose tolerance despite prior strenuous exercise. Because of this, the effect of the muscle glycogen content could not be tested. However, the results suggest that the FFA/glucose interrelationship may override exercise-induced changes in insulin-stimulated glucose uptake.     

Excessive glucose administration in severe septic patients: A possible cause of fatty degeneration in skeletal muscle tissue

The ability to oxidise fatty acids was found to be impaired in severe septic patients with multiple organ failure. Thus, glucose still represents the major substrate for total parenteral nutrition in such conditions. To evaluate the effect of a high glucose load on peripheral substrate metabolism (priming dose: 10 g/5 min, constant infusion rate: 0.5g/kg·h) we studied muscle metabolism in five patients with hypodynamic septic shock (S) using the forearm technique. Data were compared to those of five patients 3 h after elective surgery (O), who were believed to show the typical metabolic pattern of a compensated stress response. Arterial and deep venous concentrations of glucose, lactate, pyruvate, acetoacetate (AcAc), β-hydroxbutyrate (β-HOB), free fatty acids (FFA), glycerol, oxygen, insulin, adrenalin and noradrenalin were determined in the basal period and during glucose infusion.Consistent with an impaired mobilisation of endogenous substrate stores basal arterial concentrations of FFA, β-HOB and AcAc were markedly lower in severe sepsis. In O glucose infusion resulted in a continuous increase of forearm glucose uptake, compensating falling rates of FFA and ketone body uptake due to decreased arterial supply. On the contrary, in S arterial supply of FFA, AcAc and β-HOB almost remained unchanged during glucose infusion. Nevertheless, muscular balances of FFA were affected significantly, changing from a basal release into uptake during glucose infusion (basal: −0.23 ± 0.17 μmol/100 g min; 10 min of glucose infusion: 0.30 ± 0.31; 20 min: 0.95 + 0.92¹; 40 min: 0.32 ± 0.26¹; ¹: p<0.05). This was related to a marked increase in muscular glucose uptake exceeding that of O significantly. Concomitant rates of muscular glycerol release stayed low indicating reduced hydrolytic rate of muscle triglycerides.Thus peripheral lipogenesis might arise from excessive glucose administration in such conditions due to an increased rate of muscular re-esterification of FFA. To avoid this adverse side effect administration of glucose calories should be limited to basal energy requirements.     

Does glutamate influence myocardial and peripheral tissue metabolism after aortic valve replacement for aortic stenosis?

BACKGROUND & AIMS: Glutamate plays an important role for myocardial metabolism in association with ischaemia. Patients with coronary artery disease characteristically demonstrate increased uptake of glutamate. Improved recovery of myocardial metabolism and haemodynamic state after coronary surgery has been reported in patients treated with glutamate infusion. However, the effect of glutamate has not been studied after other cardiac surgical procedures. In addition, the effects of glutamate on peripheral tissue metabolism remain to be described. METHODS: Twenty patients undergoing surgery for aortic stenosis were studied after randomisation to blinded infusion of glutamate or saline during 1h immediately after skin closure. Myocardial and leg tissue metabolism were assessed with organ balance techniques. RESULTS: Postoperative glutamate infusion induced a marked increase in myocardial and leg tissue uptake of glutamate. This was associated with a significant uptake of lactate in the heart. The negative arterial-venous differences of amino acids and free fatty acids across the leg were significantly smaller in the glutamate group. Haemodynamic state remained stable and did not differ between groups. CONCLUSION: The heart and peripheral tissues consumed the exogenously administered glutamate after surgery for aortic stenosis. Potentially favourable effects of glutamate on myocardial and peripheral tissue metabolism are suggested.     

Nutrient utilisation in muscle and in the whole body of patients receiving total parenteral nutrition

Forearm metabolite exchange was assessed by the arterio-venous catheterization technique in 5 parenterally fed patients (weight 55.22 kg +/- 4.18 kg; height 1.71 m +/- 0.04 m), who received an 'all-in-one' nutrition regimen whilst in remission from Crohn's disease. All patients received 12.8 g N, 4725 kJ from carbohydrate and 4200 kJ from fat (10416 kJ total energy). The exchanges were related to nutrient oxidation and nutrient balances in the whole body as assessed by indirect calorimetry and nitrogen excretion. At rest, the subjects were found to be in positive balances for carbohydrate (+0.78 +/- 0.13 kJ/min), fat (+1.85 +/- 0.26 kJ/min) and protein (+0.240 +/- 0.04 kJ/min). Resting forearm muscle was also in positive amino acid balance and positive carbohydrate balance. Despite the large estimated uptake of glucose by forearm muscle (+1860 +/- 84 nmol/100 ml tissue/min) there was no net release of pyruvate and lactate. Glutamate and the branched chain amino acids (BCAA) were the dominant amino acids taken up by muscle (26% and 30% of total uptake respectively) and glutamine was the dominant amino acid carrying nitrogen out of muscle (78% of total amino acid nitrogen release). The energy taken up by muscle as non-esterified fatty acids, triacylglycerol and ketone bodies was small relative to that associated with glucose uptake. The results suggest that during the hypercaloric parenteral nutrition regimen, a) increased peripheral glucose uptake is not necessarily associated with increased release of glycolytic products, b) in the absence of glutamine intake for at least 10 days, muscle retains enough capacity to synthesise and release sufficient quantities of glutamine so that it remains the dominant amino acid carrying nitrogen out of muscle, c) despite the use of the intravenous route for administration of nutrients, and unusual amino acid composition of the regimen, the overall pattern of forearm metabolism bears many similarities to that which occurs after a mixed meal in normal subjects.     

High-fat diet versus habitual diet prior to carbohydrate loading: effects of exercise metabolism and cycling performance

We examined the effects of a high-fat diet (HFD-CHO) versus a habitual diet, prior to carbohydrate (CHO)-loading on fuel metabolism and cycling time-trial (TT) performance. Five endurance-trained cyclists participated in two 14-day randomized cross-over trials during which subjects consumed either a HFD (> 65% MJ from fat) or their habitual diet (CTL) (30 +/- 5% MJ from fat) for 10 day, before ingesting a high-CHO diet (CHO-loading, CHO > 70% MJ) for 3 days. Trials consisted of a 150-min cycle at 70% of peak oxygen uptake (VáO2peak), followed immediately by a 20-km TT. One hour before each trial, cyclists ingested 400 ml of a 3.44% medium-chain triacylglycerol (MCT) solution, and during the trial, ingested 600 ml/hour of a 10% 14C-glucose + 3.44% MCT solution. The dietary treatments did not alter the subjects' weight, body fat, or lipid profile. There were also no changes in circulating glucose, lactate, free fatty acid (FFA), and b-hydroxybutyrate concentrations during exercise. However, mean serum glycerol concentrations were significantly higher (p < .01) in the HFD-CHO trial. The HFD-CHO diet increased total fat oxidation and reduced total CHO oxidation but did not alter plasma glucose oxidation during exercise. By contrast, the estimated rates of muscle glycogen and lactate oxidation were lower after the HFD-CHO diet. The HFD-CHO treatment was also associated with improved TT times (29.5 +/- 2.9 min vs. 30.9 +/- 3.4 min for HFD-CHO and CTL-CHO, p <.05). High-fat feeding for 10 days prior to CHO-loading was associated with an increased reliance on fat, a decreased reliance on muscle glycogen, and improved time trial performance after prolonged exercise.     

The effect of preoperative carbohydrate loading on hormonal changes, hepatic glycogen, and glucoregulatory enzymes during abdominal surgery

The effect of preoperative glucose infusion on preoperative alterations in hepatic glycogen content, the activity of key hepatic glucoregulatory enzymes (fructose 1,6-diphosphatase [FDPase]), pyruvate kinase (PK), hormonal developments, and plasma levels of free fatty acids (FFA) were investigated in 16 patients undergoing open cholecystectomy. Patients were randomized to receive (group G) or not receive (group C) overnight glucose infusion (5 mg·kg⁻¹·d⁻¹) preoperatively. Infusion of glucose overnight resulted in preoperative elevations of insulin and c-peptide (P < 0.05) and lower plasma levels of FFA, while the same glucose levels were found in both groups, 4.6 mmol/L. During and after surgery, only minor changes in the plasma levels of insulin, c-peptide, catecholamines, glucagon, cortisol, growth hormone, and FFA were found, with minimal differences between groups. The hepatic glycogen content was 65% higher in group G and a significant reduction was confirmed only in this group of patients during surgery. The higher glycogen content was associated with a higher FDPase activity ratio (P < 0.05), which remained unchanged during surgery. In contrast, a significant (P < 0.05) increase in the activity of this enzyme was found in group C. The PK activity ratio did not differ between groups and remained unchanged during surgery. The finding of enhanced FDPase activity suggests that the indirect route (via gluconeogenesis) represents an important contributor to the increased glycogen formation during glucose infusion. Additionally, surgery in the overnight fasted patient induces enzymatic changes favoring gluconeogenesis. Lastly, preoperative high-dose glucose infusion has only minor effects on the endocrine response, plasma levels of FFA, and glycogen depletion during elective open cholecystectomy.     

Suppression of hepatic fatty acid oxidation and food intake in men

We investigated the effects of the fatty acid oxidation inhibitor etomoxir (ETO) on food intake and on fat and carbohydrate metabolism in two double-blind crossover studies in male, normal-weight subjects. In study 1, ETO (75 mg [+]-racemate) or placebo was given orally 30 min after completion of a standardized, fat-enriched (total energy: 2698 kJ, 40% from fat) lunch. The subjects (n = 15) were isolated from external time cues and free to choose when to eat dinner from an oversized serving (total energy: 6656 kJ, 60% from fat). In study 2, subjects (n = 13) were selected for habitually high fat intake (mean: 44% of energy intake). ETO (150 mg) or placebo was given after an overnight fast, 2.5 h before offering an oversized high fat breakfast (6960 kJ, 72% from fat). In both studies, blood samples were taken and the respiratory quotient (RQ) was measured several times during each test period. In study 1, ETO (75 mg) did not affect the timing and size of the dinner or subjective feelings of hunger and satiety. Although ETO (75 mg) did not affect the RQ, it decreased plasma beta-hydroxybutyrate (BHB) and increased plasma lactate compared with placebo. Plasma triacylglycerols (TG), free fatty acids (FFA), glucose, and insulin were not affected by ETO. In study 2, ETO (150 mg) enhanced hunger feelings and increased the size of the breakfast by 22.7%. ETO did not affect the RQ, but baseline RQ was lower in study 2 than in study 1 (0.83 versus 0.89, P < 0.01). Compared with placebo, ETO (150 mg) decreased plasma BHB and increased plasma FFA and plasma lactate. Baseline plasma concentrations of BHB, FFA, and lactate were higher in study 2 than in study 1 (BHB: 242 versus 81 mumol/L, P < 0.001; FFA: 0.674 versus 0.406 mmol/L, P < 0.01; lactate: 1.08 versus 0.74 mmol/L, P < 0.05). Plasma concentrations of TG, glucose, and insulin were not affected by ETO. The results suggest that inhibition of hepatic fatty acid oxidation stimulates eating in men when baseline fatty acid oxidation is sufficiently high and markedly suppressed by the treatment.     

Insufficient effect of total parenteral nutrition to improve protein balance in peripheral tissues of surgical patients.

Previous studies have indicated that unstressed and malnourished patients do not necessarily obtain amino acid balance across peripheral tissues during total parenteral nutrition (TPN) treatment, indicating treatment inefficiency. Therefore, the aim of this study was to evaluate to what extent (prevalence) insufficient therapeutic amino acid balance occurs in surgical patients receiving TPN for standard medical reasons. Thirty-two patients treated in an ordinary surgical ward (n = 17) or in the intensive care unit (ICU) (n = 15) were examined. The arteriovenous balance across the leg of amino acids, glucose, glycerol, lactate, and oxygen was measured in relationship to plasma levels of insulin. All patients had been receiving TPN for at least 7 days before the investigation. All measurements were performed when amino acids had been infused for at least 4 hours and thus expected to support the resynthesis of lean body mass. Patients treated in the ICU and the surgical ward were in positive whole-body energy balance (+1127 +/- 121 and +917 +/- 123 kcal, respectively). Glucose uptake and oxygen consumption across the leg were similar in both patient groups. Glycerol release was not different from zero balance, indicating that inhibition of lipolysis across the leg during feeding and lactate was normally released in both groups. However, approximately 50% of the patients treated in the ordinary ward and 80% to 100% of the patients in the ICU remained in negative amino acid balance across the leg as judged from significant release of either methionine, tyrosine, or phenylalanine despite concomitant infusion of amino acids (approximately 0.3 g of N per kilogram per day) and nonprotein calories.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin sensitivity in septic cancer-bearing patients.

Resistance to insulin's effect on glucose metabolism is a well-documented phenomenon. The magnitude of resistance to insulin's antilipolytic action is usually less than the resistance to insulin's action on glucose metabolism. In sepsis, resistance to the antilipolytic effect of insulin may be more prominent than resistance to insulin's action on glucose metabolism. Therefore, free fatty acid (FFA) turnover, FFA concentration, glucose tissue uptake, and endogenous glucose production were measured in nine septic cancer-bearing patients and six healthy volunteers during a constant glucose load at two different insulin concentrations. During infusion of glucose alone, plasma insulin concentration in patients and control subjects were, respectively 33 +/- 7 mU/L and 23 +/- 4 mU/L. When plasma glucose was clamped at the low normal range these values were, respectively, 85 +/- 17 mU/L and 28 +/- 5 mU/L (p less than 0.05). Glucose tissue uptake and endogenous glucose production were not significantly different in patients and control subjects in both parts of the study. FFA turnover and FFA concentrations were significantly higher in the patients compared with the control subjects (p less than 0.001) in both parts of the study. It is concluded that in septic cancer-bearing patients, resistance to insulin's effect on FFA turnover is more pronounced than resistance to its inhibiting effect on endogenous glucose production and its stimulating effect on glucose tissue uptake.     

Arterio-venous differences in amino acids, glucose, lactate and fatty acids in burn patients; effect of ornithine alpha-ketoglutarate

The study concerns two groups of seven burn patients matched for age, weight and total burn surface. Both groups received conventional enteral nutrition, while one was given a 10 g/day alpha-ketoglutarate ornithine (OKG) supplement. Femoral venous and arterial blood was taken from day 2 to day 13 post-burn in order to determine levels of amino acids, nonesterified fatty acids (NEFA), glucose and lactate. In the control group large negative arterio-venous differences (DeltaA-V) were observed in amino acid and lactate levels whereas they were significantly lower with regard to Hyp, Gly, Lys and Ala in the OKG-treated group. DeltaA-V was near zero for glucose and NEFA in both groups. These results support the view that OKG-therapy limits the output of amino acids in the leg and that glucose and NEFA do not constitute the main fuel in muscle.     

Physiologic growth hormone replacement improves fasting lipid kinetics in patients with HIV lipodystrophy syndrome

BACKGROUND: HIV lipodystrophy syndrome (HLS) is characterized by accelerated lipolysis, inadequate fat oxidation, increased hepatic reesterification, and a high frequency of growth hormone deficiency (GHD). The effect of growth hormone (GH) replacement on these lipid kinetic abnormalities is unknown. OBJECTIVE: We aimed to measure the effects of physiologic GH replacement on lipid kinetics in men with HLS and GHD. DESIGN: Seven men with HLS and GHD were studied with the use of infusions of [13C1]palmitate, [2H5]glycerol, and [2H3]leucine to quantify total and net lipolysis, palmitate and free fatty acid (FFA) oxidation, and VLDL apolipoprotein B-100 synthesis before and after 6 mo of GH replacement (maximum: 5 microg x kg(-1) x d(-1)). RESULTS: GH replacement decreased the rates of total lipolysis [FFA(total) rate of appearance (x +/- SE): from 4.80 +/- 1.24 to 3.32 +/- 0.76 mmol FFA x kg fat(-1) x h(-1); P < 0.05] and net lipolysis (FFA(net) rate of appearance: from 1.87 +/- 0.34 to 1.20 +/- 0.25 mmol FFA x kg fat(-1) x h(-1); P < 0.05). Fat oxidation decreased (from 0.28 +/- 0.02 to 0.20 +/- 0.02 mmol FFA x kg lean body mass(-1) x h(-1); P < 0.002), as did the rate of appearance of FFAs available for intrahepatic reesterification (from 0.50 +/- 0.13 to 0.29 +/- 0.09 mmol FFA x kg fat(-1) x h(-1); P < 0.03). Fractional and absolute synthetic rates of VLDL apolipoprotein B-100 were unaltered. These kinetic changes were associated with a decrease in the waist-to-hip ratio but no significant change in fasting plasma lipid concentrations. Fasting plasma glucose concentrations increased after treatment (from 5.2 +/- 0.2 to 5.8 +/- 0.3 mmol/L; P < 0.01). CONCLUSIONS: Physiologic GH replacement has salutary effects on abnormal lipid kinetics in HLS. The effects are mediated by diminished lipolysis and hepatic reesterification rather than by increased fat oxidation.     

Comparative effects of fructose and glucose on the lipid and carbohydrate metabolism of perfused rat liver.

1. Livers from rats fed on a standard diet were perfused with whole blood, and infused continuously with glucose and fructose at equimolar rates. 2. Infusion of fructose increased both the secretion of very-low-density-lipoprotein (VLDL)-triglycerides and the incorporation of free fatty acids (FFA) from the perfusate into VLDL-lipids, but neither of these two processes was affected by infusion of glucose. 3. Infusion of fructose decreased the oxidation and increased the esterification of FFA, but glucose infusion had no effect on these processes. When fructose and glucose were infused together was a further decrease in oxidation. 4. When fructose was infused alone or together with glucose, blood concentrations rapidly became stabilized at those found in the hepatic portal vein in vivo, with similar rates of hepatic uptake to those found in the intact animal. Infusion of glucose alone resulted in continuously increasing perfusate glucose concentrations, and rates of uptake which were only 20% of those for fructose. Blood glucose concentrations were reduced, and lactate concentrations were increased by fructose infusion, and when glucose and fructose were infused together there was a greatly increased rate of glucose uptake. 5. Liver glycogen was not affected by the infusion of fructose or glucose alone; however, their combined addition significantly increased its concentration. 6. Uptake of perfusate FFA was not affected by either fructose or glucose infusions. 7. The results are discussed in terms of the differences in nutrition and metabolism between glucose and fructose, with particular reference to the development of hypertriglyceridaemia.     

Impact of enteral and parenteral nutrition on hepatic and muscle glucose metabolism

Liver and muscle metabolism were assessed in dogs adapted to long-term total parenteral (TPN) and enteral (TEN) nutrition. Studies were done in 13 conscious long-term catheterized dogs in which sampling (artery, portal and hepatic vein, and iliac vein), infusion catheters (inferior vena cava, duodenum), and transonic flow probes (hepatic artery, portal vein, and iliac artery) were implanted. Fourteen days after surgery dogs were grouped to receive TPN or TEN. After 5 days of TPN/TEN, substrate balances across the liver and limb were assessed. The liver was a marked net consumer of glucose in both groups (23.6 +/- 3.3 vs 22.6 +/- 2.8 micromol x kg(-1) x min(-1), TPN vs TEN) despite near normoglycemia (6.5 +/- 0.3 vs 6.7 +/- 0.2 mmol/L). Arterial insulin levels were higher during TEN (96 +/- 6 vs 144 +/- 30 pmol/L; p < .05). The majority (79 +/- 13 vs 76% +/- 7%) of the glucose taken up by the liver was released as lactate. Despite higher insulin levels during TEN the nonsplanchnic tissues consumed a lessor quantity of glucose (25.9 +/- 3.3 vs 16.1 +/- 3.9 micro x mol x kg(-1) x min(-1)). In summary, the liver undergoes a profound adaptation to TPN and TEN making it a major site of glucose uptake and conversion to lactate irrespective of the route of nutrient delivery. However, the insulin requirements are higher with TEN possibly secondary to impaired peripheral glucose removal.     

Effects of short-chain fructo-oligosaccharides on glucose and lipid metabolism in mild hypercholesterolaemic individuals

BACKGROUND: The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism. AIM: To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia. Design: A randomized double-blind sequential cross-over study. SUBJECTS AND METHODS: Thirty subjects of both genders (20 M/10 F), mean age 45.5+/-9.9 years (M+/-SD), BMI 26.6+/-2.2 kg/m(2), with plasma cholesterol >5.17 and <7.76 mmol/l and plasma triglycerides <3.45 mmol/l, participated in the study. The study was performed after a wash-out period of 1 month and a run-in period of 1 month to stabilize patients on a standard diet (CHO 50%, fat 30%, protein 20%, fibre 20 g/day) plus placebo (maltodextrine plus aspartame 15 g/day). At the end of run-in, subjects were randomly assigned to receive sc-FOS (Actilight) (10.6g/day) or placebo (maltodextrine plus aspartame 15 g/day) with tea and/or coffee for a duration of 2 months and thereafter switched to the other treatment for additional 2 months. Plasma glucose, total and lipoprotein (VLDL, LDL, HDL) cholesterol and triglyceride concentrations were measured in the fasting state at the end of run-in and of each treatment period. At the end of the two treatment periods, patients consumed a standard test meal (protein 15%, carbohydrate 34%, fat 51%, kJ 3988) 1h after the administration of 5.3g of sc-FOS or placebo; plasma glucose, insulin, free fatty acid (FFA) and triglyceride responses to the test meal were evaluated. RESULTS: No significant difference in fasting parameters was detected between the two treatments. After sc-FOS and placebo plasma cholesterol levels were, respectively, 6.47+/-0.70 and 6.44+/-0.78 mmol/l (n.s.) and plasma triglycerides were 1.53+/-0.71 and 1.56+/-0.53 mmol/l (n.s.). No significant differences were observed in cholesterol and triglyceride content of VLDL, LDL and HDL and in plasma Apo A1 levels; conversely, fasting plasma Lp(a) concentrations were significantly increased after sc-FOS (37+/-38 vs. 33+/-35 mg/dl; P<0.005). Postprandial responses of glucose, FFA and triglycerides were not significantly different between sc-FOS and placebo, while postprandial insulin response (incremental area) was significantly reduced after sc-FOS compared to placebo (14,490+/-7416 vs. 17,760+/-7710 pmol/l x 300 min; P<0.02). CONCLUSIONS: A moderate intake of sc-FOS has no major effects on lipid metabolism, both in the fasting and in the postprandial period, in individuals with mild hypercholesterolaemia. A small but significant increase of Lp(a) concentrations was observed with sc-FOS consumption together with a reduction of the postprandial insulin response; however, the clinical relevance of these small effects is unclear.     

游离脂肪酸对肝细胞ACSL1表达及相关脂代谢的影响

目的研究游离脂肪酸(FFA)的诱导对L02肝细胞长链脂酰CoA合成酶1(ACSL1)的表达及相关代谢的影响。方法用含不同浓度(0.2、0.4、0.8 mmol/L)FFA的培养液诱导L02细胞48 h,Western blot检测ACSL1蛋白水平,荧光定量PCR检测ACSL1 mRNA水平,比色法测定甘油三酯(TG)含量、ATP水平和培养上清FFA浓度变化,生化法测定酮体含量和培养上清葡萄糖浓度变化。结果 FFA的诱导可显著提高ACSL1蛋白表达水平(P<0.01),但对ACSL1 mRNA水平无明显影响(P>0.05),细胞内TG含量显著升高(P<0.01或P<0.05),酮体含量显著升高(P<0.05),培养上清葡萄糖消耗显著增加(P<0.01),胞内ATP水平无明显变化(P>0.05),与0.2 mmol/L、0.4 mmol/L FFA组相比,0.8 mmol/L FFA组培养上清FFA消耗显著增加(P<0.01或P<0.05)。结论 FFA通过上调ACSL1蛋白表达水平致肝细胞TG蓄积。     

Accelerated splanchnic amino acid uptake after cardiac surgery

Energy expenditure increases after cardiac surgery, but changes in peripheral tissue metabolism do not explain this increase. We hypothesized that the splanchnic region is a major contributor to the postoperative hypermetabolism, and this should be reflected in the exchange of amino acids across the splanchnic bed. We measured systemic and regional (splanchnic and leg) amino acid exchange, oxygen uptake and hemodynamics in 22 elective coronary bypass grafting patients postoperatively after arrival to the intensive care unit, 2 h later, and after stabilization of hemodynamics. Splanchnic uptake of glutamine (50 +/- 37 micromol/min/m2 to 78 +/- 37 micromol/min/m2, P < 0.05) and three of the gluconeogenetic amino acids, alanine (115 +/- 52 micromol/min/m2 to 183 +/- 70 micromol/min/m2, P < 0.05), serine (18 +/- 10 micromol/min/m2 to 26 +/- 13 micromol/min/m2) and threonine (20 +/- 8 micromol/min/m2 to 28 +/- 8 micromol/min/m2) increased during the observation period. Similarly, the oxygen consumption by the splanchnic region increased while splanchnic blood flow remained stable. A correlation between oxygen and amino acid uptake by the splanchnic bed was observed during the study period. Femoral exchange of glutamine and alanine did not change, although femoral blood flow and oxygen consumption increased during rewarming. High metabolic activity was observed in the splanchnic region during the early postoperative phase after hypothermic cardiac surgery. The increased plasma amino acid concentration indicates a release of amino acids from other sources than the peripheral muscle.     

Dietary protein level and energy metabolism during treadmill exercise in horses

Six conditioned Quarter Horse mares were used in a crossover design to assess the effect of the dietary protein level on intramuscular and hepatic glycogen and lactate, oxygen uptake and blood lactate, pyruvate and free fatty acids. After a 2-wk adaptation period to either a 9.0% (control) or an 18.5% crude protein diet, each horse performed an exercise test. The horses were exercised for 15 min on an 11% grade treadmill at 4.5 m/sec. The exercise test was performed 3-4 h after a meal. Venous, arterial and mixed-venous blood samples were taken simultaneously at rest and during exercise. Muscle and liver samples were taken at rest and after exercise. The dietary protein level did not affect hepatic or intramuscular glycogen utilization (P greater than 0.05). Exercise resulted in increased (P less than 0.001) lactate in venous blood, muscle and liver; however, dietary treatment did not affect (P greater than 0.05) lactate level. Venous blood lactate:pyruvate ratio was higher (P less than 0.05) in the control horses. Dietary protein level did not affect (P greater than 0.05) oxygen uptake or plasma free fatty acids; however, exercise increased (P less than 0.01) both. These results indicate the dietary protein did not affect substrate utilization during the absorptive phase of digestion in exercising horses; however, the higher lactate:pyruvate ratio in the control horses suggests that the intraconversion of lactate and pyruvate may be influenced by diet composition.