Ethanol causes acute inhibition of carbohydrate, fat, and protein oxidation and insulin resistance.

To study the mechanism of the diabetogenic action of ethanol, ethanol (0.75 g/kg over 30 min) and then glucose (0.5 g/kg over 5 min) were infused intravenously into six normal males. During the 4-h study, 21.8 +/- 2.1 g of ethanol was metabolized and oxidized to CO2 and H2O. Ethanol decreased total body fat oxidation by 79% and protein oxidation by 39%, and almost completely abolished the 249% rise in carbohydrate (CHO) oxidation seen in controls after glucose infusion. Ethanol decreased the basal rate of glucose appearance (GRa) by 30% and the basal rate of glucose disappearance (GRd) by 38%, potentiated glucose-stimulated insulin release by 54%, and had no effect on glucose tolerance. In hyperinsulinemic-euglycemic clamp studies, ethanol caused a 36% decrease in glucose disposal. We conclude that ethanol was a preferred fuel preventing fat, and to lesser degrees, CHO and protein, from being oxidized. It also caused acute insulin resistance which was compensated for by hypersecretion of insulin.     

Thermic response to isoenergetic protein, carbohydrate or fat meals in lean and obese subjects

The thermic response of five lean and five obese subjects was measured by indirect calorimetry before, and for 157.5 min after a meal of protein, carbohydrate or fat, each of which provided 1.25 MJ. The change in plasma glucose, insulin and (in the case of the carbohydrate meal) the rate of exogenous glucose oxidation was also measured. There was no significant difference between the lean and obese groups in the magnitude of the thermic response to any of the three meals. In both weight groups the response was largest and most prolonged after the protein meal (P less than 0.01). The obese group showed a higher concentration of fasting plasma insulin (P less than 0.01) and a larger increase in plasma glucose (P less than 0.05) after the carbohydrate meal, but there was no significant difference in the oxidation of exogenous glucose when compared with the lean group. Previous studies on dietary-induced thermogenesis in lean and obese subjects have given conflicting results. In general reports of decreased thermogenesis in obese subjects are characterized by either (a) high pre-meal metabolic rates in the obese group, especially in diabetic subjects, or (b) a group classified as 'normal' who have been selected for their high thermogenic capacity.     

Effect of dietary fat, carbohydrate, and protein on branched-chain amino acid catabolism during caloric restriction.

To assess the effect of each dietary caloric source on the catabolism of branched-chain amino acids, we investigated the rate of leucine oxidation before and after obese volunteers consumed one of the following diets for one week: (a) starvation, (b) 300 or 500 cal of fat/d, (c) 300 or 500 cal of carbohydrate/d, (d) 300 or 500 cal of protein/d, (e) a mixture of carbohydrate (300 cal/d) and fat (200 cal/d), or (f) a mixture of carbohydrate (300 cal/d) and protein (200 cal/d). Starvation significantly increased the rate of leucine oxidation (1.4 +/- 0.11 vs. 1.8 +/- 0.16 mmol/h, P less than 0.01). The same occurred with the fat and protein diets. In sharp contrast, the 500-cal carbohydrate diet significantly decreased the rate of leucine oxidation (1.3 +/- 0.13 vs. 0.6 +/- 0.09 mmol/h, P less than 0.01). The same occurred when a portion of the carbohydrate diet was isocalorically replaced with either fat or protein. The cumulative nitrogen excretion during the fat diet and starvation was not significantly different. As compared with the fat diets, the carbohydrate diets on the average reduced the urinary nitrogen excretion by 12 g/wk. Nitrogen balance was positive during the consumption of the 500-cal protein diet, but negative during the consumption of carbohydrate-protein diet. The fat diets, like the protein diets and starvation, greatly increased plasma leucine (119 +/- 13 vs. 222 +/- 15 microM, P less than 0.01) and beta-hydroxybutyrate (0.12 +/- 0.02 vs. 4.08 +/- 0.43 mM, P less than 0.01) concentrations, and significantly decreased plasma glucose (96 +/- 4 vs. 66 +/- 3 mg/dl, P less than 0.01) and insulin (18 +/- 4 vs. 9 +/- 1 microU/ml, P less than 0.05) concentrations. These changes did not occur, or were greatly attenuated, when subjects consumed carbohydrate alone or in combination with fat or protein. We conclude that during brief caloric restriction, dietary lipid and protein, unlike carbohydrate, do not diminish the catabolism of branched-chain amino acids and the decrease in branched-chain amino acid oxidation is associated with protein sparing.     

Effects of dopexamine in comparison with fenoterol on carbohydrate,fat and protein metabolism in healthy volunteers

Objective In critically ill patients adrenergic agonists are used to treat haemodynamic disorders. Their metabolic actions should be considered in controlling metabolic homeostasis. Dopexamine has assumed effects on carbohydrate, fat and protein metabolism. The aim of this study was to define its metabolic actions and compare these with those of fenoterol by using a stable isotope dilution technique.Design Prospective, randomized experimental study.Setting Experimental section of a university anaesthesiology department.Participants Twenty-seven healthy male volunteers in three groups with nine participants each.Interventions Participants received a 4-h infusion of dopexamine (2.25 µg/kg per min), fenoterol (at least 0.025 µg/kg per min) or saline.Measurements and results Before and every 80 min during drug infusion, we measured endogenous glucose production and the plasma appearance rates for leucine and urea. In addition, we measured plasma concentrations of glucose, lactate, free fatty acids (FFAs), noradrenaline, adrenaline, insulin, glucagon and potassium. Endogenous glucose production did not differ among the groups. Glucose plasma concentration and glucose clearance remained constant during the dopexamine infusion. Fenoterol increased glucose plasma concentration and decreased glucose clearance. Lactate, FFAs, insulin and noradrenaline plasma concentrations were increased and the rate of leucine appearance was decreased by both drugs. The rate of urea appearance did not differ from the control group.Conclusions Dopexamine has no or only weak effects on carbohydrate metabolism, its effects on fat and protein metabolism are comparable to those of fenoterol. This metabolic profile may be advantageous in increasing cardiac output in patients with impaired glucose tolerance.     

运动对糖、脂代谢的影响

本文通过对运动营养研究中有关运动中碳水化合物补给与脂肪动员氧化等热点问题的概述,分别介绍了运动对糖、脂代谢影响研究中的新观点与运动中糖脂代谢的相互影响。     

Effects of dietary fat on postprandial substrate oxidation and on carbohydrate and fat balances.

To study the effect of dietary fat on postprandial substrate utilization and nutrient balance, respiratory exchange was determined in seven young men for 1 h before and 9 h after the ingestion of one of three different breakfasts: i.e., bread, jam, and dried meat (482 kcal: 27% protein, 62% carbohydrate, and 11% fat); bread, jam, and dried meat plus 50 g of margarine containing long-chain triglycerides (LCT); or bread, jam, and dried meat plus 40 g medium-chain triglycerides (MCT) and 10 g LCT margarine (858 kcal: 15% protein, 35% carbohydrate, and 50% fat). Plasma glucose concentrations peaked 45 min after the start of the meals. When compared with the low fat meal, the LCT margarine supplement had no effect at any time on circulating glucose and insulin concentrations, nor on the respiratory quotient. When MCTs were consumed, plasma glucose and insulin concentrations remained lower and plasma FFA concentrations higher during the first 2 h. 9 h after the breakfasts, the amounts of substrates oxidized were similar in each case, i.e., approximately 320, 355, and 125 kcal for carbohydrate, fat, and protein, respectively. This resulted in comparable carbohydrate (mean +/- SD = -22 +/- 32, -22 +/- 37, and -24 +/- 22 kcal) and protein balances (-7 +/- 9, +7 +/- 7, and -8 +/- 11 kcal) after the low fat, LCT- and MCT-supplemented test meals, respectively. However, after the low fat meal, the lipid balance was negative (-287 +/- 60 kcal), which differed significantly (P less than 0.001) from the fat balances after the LCT- and MCT-supplemented meals, i.e., +60 +/- 33 and +57 +/- 25 kcal, respectively. The results demonstrate that the rates of fat and of carbohydrate oxidation are not influenced by the fat content of a meal.     

High fat,low carbohydrate,enteral feeding in patients weaning from the ventilator

Objective To study whether high fat, low carbohydrate enteral nutrition could reduce in patients during ventilator support and weaning from the ventilator in order to facilitate the weaning process.Design Prospective, randomized controlled study.Setting Medical ICU of a university hospital.Patients 32 ventilator-dependent patients with a prospect of weaning from mechanical ventilation.Interventions High fat feeding administered to 15 patients and standard isocaloric feeding administered to 17 patients, both in a dosage of 1.5 times basal metabolic rate.Measurements and results Respiratory and metabolic measurements were obtained both during mechanical ventilation and weaning procedures. High fat feeding was associated with significantly lower RQ values compared with standard feeding; the mean (±SEM) RQ values during mechanical ventilation amounted to 0.91±0.01 and 1.00±0.02 and during weaning to 0.72±0.02 and 0.86±0.02 for high fat and standard nutrition respectively (bothp-values<0.001). High fat feeding reduced the CO₂-excretion both during mechanical ventilation and weaning, but only the decrease during weaning proved to be significant; the mean (±SEM) CO₂-excretion amounted to 0.177±0.010 and 0.231±0.011 l/min STPD for the high fat and standard feeding respectively (p<0.01). No significant differences were found in the PaCO₂ during weaning between the two feeding groups.Conclusion High fat, low carbohydrate enteral feeding significantly reduced the RQ values in ventilated patients with decreases , but in this study failed to reduce PaCO₂ during weaning from the ventilator.     

高脂低碳水化合物膳食模式对肥胖大鼠影响的研究

目的探讨高脂低碳水化合物膳食模式对肥胖大鼠影响。方法利用膳食模式建立营养性肥胖大鼠模型100只,用随机数字表法按体重分层随机分为普通饲料对照组20只(9.0%脂肪,78%碳水化合物)、高脂饲料组80只(70%脂肪,16%碳水化合物)。每天称进食量;每周称大鼠体重;第3和第11周测血脂;第10周进行口服葡萄糖耐量试验和胰岛素释放试验、第11周测瘦素和酮体。结果两组大鼠原摄食标准为85 g/3 d,对照组大鼠3 d内85 g食物全部食用,观察组大鼠摄食量明显下降,摄入能量减少,且与对照组比较差异有统计学意义(P0.05);观察组大鼠高脂低碳水化合物膳食模式进行第28天、第35天、第42天、第56天、第70 d体重增长明显,且与对照组同时间段比较差异均有统计学意义(P0.05);观察组大鼠高脂低碳水化合物膳食模式进行到第9周后甘油三酯(TG)、总胆固醇(TC)明显高于对照组同期水平、而高密度脂蛋白胆固醇(HDL-C)明显低于对照组,且差异均有统计学意义(P0.05);与对照组比较,观察组大鼠高脂低碳水化合物膳食模式进行70 d后,体重、脂肪垫重、Lee氏指数、脂肪体比等指标明显升高,脾体比明显降低,差异均有统计学意义(P0.05);观察组大鼠观察组在15 min餐后血糖水平明显高于对照组,且与比较差异有统计学意义(P0.05);两组大鼠喂养70 d后瘦素、酮体等指标比较差异无统计学意义(P0.05)。结论高脂低碳水化合物膳食模式使大鼠对脂代谢的调节能力下降,出现血脂紊乱。     

Metabolism of fat emulsions by thermally injured patients

The lipolytic capacity of patients with severe and moderate thermal injury was assessed in vivo by determining the rate of clearance of chylomicrons. Twelve patients, two women and ten men, age 34 +/- 12 years, had burns varying from 28% to 84% of total burn surface area (TBSA). Seven patients had an average burn size of 63% TBSA. They were hypocholesterolemic and normotriglyceridemic during parenteral alimentation that excluded fat emulsion. But when Lyposil was infused intravenously (150 mg/kg/hr for a period of eight hrs), plasma triglyceride (TG) levels increased. Most of the triglyceride was in the form of chylomicrons, which had a prolonged residence time in plasma. Patients with moderate thermal injury (mean % TBSA 38% +/- 9%) had normal TG levels before fat infusion. When Liposyl was infused intraduodenally (170 mg/kg/hr), the plasma TG levels remained normal and the chylomicron half-life was very short. These observations suggest that patients with severe thermal injury may have reduced lipolytic capacity, especially during parenteral administration of fat emulsion.     

Relationship of body fat distribution to blood pressure, carbohydrate tolerance, and plasma lipids in healthy obese women

In 110 obese, healthy women, a relationship was sought between distribution of body fat and blood pressure, glucose tolerance, plasma insulin, and fasting plasma lipid and serum uric acid concentrations. The index of body fat distribution was the ratio of waist circumference to hips circumference (WHR). The WHR range in this group was 0.5 to 0.99, with a median value of 0.78. Positive, significant correlations were found between WHR and both systolic and diastolic blood pressure and between WHR and the total integrated plasma glucose and insulin responses during 4 hr oral glucose tolerance tests. No relationship was found between WHR and age, the degree of obesity as defined by the weight-to-height ratio, or concentrations of fasting plasma free fatty acids, plasma triglyceride, plasma cholesterol, or serum uric acid. Subsequently, 27 women in the highest quartile of the WHR range (0.83 to 0.99) were compared to 28 age- and weight-matched subjects in the lowest quartile of WHR (0.5 to 0.73). Women in the highest quartile had systolic and diastolic blood pressure as well as total plasma glucose and insulin responses during glucose tolerance tests that significantly exceeded mean values of subjects in the lowest quartile. We conclude that in healthy, obese women, a continuum exists that relates increasing fat accumulation in the upper body to progressively higher blood pressure, reduced carbohydrate tolerance, and higher plasma insulin concentrations. These changes occurred independently of age of degree of obesity in this population.     

Effects of fat on insulin-stimulated carbohydrate metabolism in normal men.

We have examined the onset and duration of the inhibitory effect of an intravenous infusion of lipid/heparin on total body carbohydrate and fat oxidation (by indirect calorimetry) and on glucose disappearance (with 6,6 D2-glucose and gas chromatography-mass spectrometry) in healthy men during euglycemic hyperinsulinemia. Glycogen synthase activity and concentrations of acetyl-CoA, free CoA-SH, citrate, and glucose-6-phosphate were measured in muscle biopsies obtained before and after insulin/lipid and insulin/saline infusions. Lipid increased insulin-inhibited fat oxidation (+40%) and decreased insulin-stimulated carbohydrate oxidation (-63%) within 1 h. These changes were associated with an increase (+489%) in the muscle acetyl-CoA/free CoA-SH ratio. Glucose disappearance did not decrease until 2-4 h later (-55%). This decrease was associated with a decrease in muscle glycogen synthase fractional velocity (-82%). The muscle content of citrate and glucose-6-phosphate did not change. We concluded that, during hyperinsulinemia, lipid promptly replaced carbohydrate as fuel for oxidation in muscle and hours later inhibited glucose uptake, presumably by interfering with muscle glycogen formation.     

Postprandial triglycerides in response to high fat: role of dietary carbohydrate

BACKGROUND: The postprandial triglyceride response following a meal high in fat (HFM) has been related to atherogenesis and insulin resistance. We examined the influence of dietary carbohydrate and the accompanying insulin secretory response on the postprandial triglyceride response following a HFM. MATERIALS AND DESIGN: High-fat meals of equal fat content (fat 80 g) containing either 20 g (low) or 100 g (high) of carbohydrate (HFM-LC and HFM-HC, respectively), and therefore not isocaloric (4250 kJ of HFM-LC and 5450 kJ of HFM-HC), were consumed by seven (four male, three female) normolipidaemic subjects (aged 32.9 +/- 3.7 years, BMI 24.7 +/- 1.8 kg m-2). Blood and indirect calorimetry data were collected at 0-4 h. RESULTS: HFM-HC produced a significant rise in plasma glucose (Delta0.54 +/- 0.23 mmol L-1, P = 0.05) at 2 h, while a HFM-LC elicited no mean change from baseline. Following a HFM-LC, the plasma insulin incremental area under the curve (AUC) was significantly lower (31.3 +/- 6.7 vs. 83.2 +/- 11.9 mU l-1 h-1, P < 0.0003) and the postprandial triglyceride response AUC was significantly greater (1.66 +/- 0.36 vs. 1.24 +/- 0.31 mmol L-1 h-1, P < 0.006) compared with a HFM-HC. Plasma free fatty acids were suppressed by 44% (P = 0.04) and 66% (P < 0.0001) at 1 h following HFM-LC and HFM-HC, respectively, compared with baseline. There were no significant differences between the meals in energy expenditure, substrate oxidation rates, or respiratory quotient responses. CONCLUSIONS: By design, the HFMs were not isocaloric but the presence of carbohydrate in a HFM invoked an insulin response that significantly reduced the 4 h postprandial triglyceride response even in healthy, normolipidaemic subjects. This phenomenon may have clinical implications, particularly in relation to insulin sensitivity.     

High fat,low carbohydrate,enteral feeding lowers PaCO2 and reduces the period of ventilation in artificially ventilated patients

The objective of this study was to compare the effect of a high fat, low carbohydrate enteral feed with a standard isocaloric, isonitrogenous enteral feed on PaCO₂ and ventilation time in patients with acute respiratory failure requiring artificial ventilation. 20 clinically stable patients requiring enteral feeding were randomized to either feed in a double-blind fashion. Initial ventilator standard settings were adjusted according to clinical state. Measurements including minute volume and arterial blood gases were made twice daily. Weaning was carried out according to set criteria. During the feeding period, PaCO₂ just prior to weaning fell by 16% in the high fat group but increased by 4% in the standard feed group (p=0.003). The high fat group spent a mean of 62 h less time on the ventilator (p=0.006). A high fat, low carbohydrate enteral feed appears to be beneficial in patients undergoing artificial ventilation.     

Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet.

A new experimental approach was used to determine whether a eucaloric, low fat, high carbohydrate diet increases fatty acid synthesis. Normally volunteers consumed low fat liquid formula diets (10% of calories as fat and 75% as glucose polymers, n = 7) or high fat diets (40% of calories as fat and 45% as glucose polymers, n = 3) for 25 d. The fatty acid composition of each diet was matched to the composition of each subject's adipose tissue and compared with the composition of VLDL triglyceride. By day 10, VLDL triglyceride was markedly enriched in palmitate and deficient in linoleate in all subjects on the low fat diet. Newly synthesized fatty acids accounted for 44 +/- 10% of the VLDL triglyceride. Mass isotopomer distribution analysis of palmitate labeled with intravenously infused 13C-acetate confirmed that increased palmitate synthesis was the likely cause for the accumulation of triglyceride palmitate and "dilution" of linoleate. In contrast, there was minimal fatty acid synthesis on the high diet. Thus, the dietary substitution of carbohydrate for fat stimulated fatty acid synthesis and the plasma accumulation of palmitate-enriched, linoleate-deficient triglyceride. Such changes could have adverse effects on the cardiovascular system.