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The effects of starvation and infused adrenaline on fatty acid turnover and oxidation in man
POSTER PRESENTATIONS Topic 2 - LIPID
AND CARBOHYDRATE
P.1 Influence of an euglycaemic hyperinsulinaemic clamp on plasma elimination rate and utilisation of exogenous fat - determined by hypertriglyceridaemic clamp technique. A. Thiirne, J. Nordenstrtim and A. Alvestranti. Departments of Surgery and *Rena/ University Hospitaal, Sweden.
Medicine,
METABOLISM
energy source by the body. The purposes of the present study were to examine the relationship between plasma fatty acid turnover and oxidation after short periods of fasting and to see how adrenaline infusion affected these processes. Nine healthy subjects (mean age 22.9 f 1.2 (SE) years, body mass index 22.0 t 0.80 kg/m’) were recruited. Each attended after 12, 36 and 72 hrs of fasting, with the studies done in random order. Basal blood samples were taken for measurement of plasma palmitate concentration and (1 ,‘3C]-palmitate enrichment using mass spectrometry. Expired air was was sampled for analysis of 13C02 enrichment. A NaH13C0, bolus was given and a [l ,‘3C]-palmitate infusion commenced with blood and air samples obtained after 45min. Adrenaline was then infused at 2.5 ng min-’ kg ideal body weight-’ for 90 minutes, whilst the [1,‘3C]-palmitate was continued, with further samples taken at IO min intervals. Indirect calorimetry was performed throughout. Basal palmitate turnover increased with duration of fasting from 1.48 + 0.22 to 1.95 rt 0.34 to 2.26 I 0.33mmolmin-’ kg body weight-’ after 12, 36 and 72 hrs respectively (P < 0.01, ANOVA). Basal plasma palmitate oxidation also rose from 0.64+0.09 to 0.85 + 0.16 to 0.83&0.11 mmol min” kg body weight-’ (P < 0.05, ANOVA). The proportion of plasma palmitate turnover which was oxidised was unaffected by fasting (44 * 2, 46 f 5 and 42 ? 4% respectively). In response to adrenaline the peak plasma palmitate turnovers were 2.31 + 0.36, 2.79 f 0.67 and 2.97 + 0.73 mmol mini’ kg body weight-’ respectively, there being no significant effect of fasting on the magnitude of the response. By the end of the adrenaline infusion the percent of turnover which was oxidised had fallen to 34 f 3% (12 hrs), 36 + 4% (36 hrs) and 25 f 4% (72 hrs). In the basal state fasting leads to increased lipolysis and fat oxidation, However, fasting has no effect on the percent of plasma fatty acid turnover which is oxidised. Adrenaline infusion appears to favour intratissue lipid oxidation over plasma lipid oxidation. The oxidation of skeletal muscle fat stores may be responsible for skeletal muscle thermogenesis and the enhanced thermogenic response to adrenaline seen after fasting.
Huddinge
Previous studies have suggested that the plasma insulin concentration is the major determinant for the rate of lipolysis but it is less clear whether the insulin niveau is important for the plasma elimination rate of exogenous fat. The purpose of the present study was to examine the possible influence of glucose and insulin administration on the elimination rate and utilisation of a fat emulsion by using indirect calorimetry (IC), hypertriglyceridaemic (HTG) and euglycaemic hyperinsulinaemic (EH) clamp techniques. The HTG and EH clamps and the indirect calorimetry were performed as follows: A priming dose of a LCT emulsion 13 mg triglycerides (TG)/kg BW x min was given in order to reach a TG concentration of 4 mmol/l. The infusion rate was adjusted to maintain TG at 4 mmolll during 180 min. The infusion rate of lipids during the steady state (at 180 min) reflects the plasma elimination rate of exogenous fat. After a bolus dose insulin was administered simultaneously with the lipids by a constant infusion of 20mUtm’ BSA x min. The glucose level was maintained at 8 mmol/l during the steady state period by adjustment of the infusion rate of a 20% glucose solution. Continuous IC was carried out in the basal state and then throughout the study period. Ten healthy male volunteers with an average age of 30 years (24-44yrs) and a body mass index 24 (21-26) were randomly allocated for two treatment order groups in an open, cross-over study. The subjects were studied on two occasions, once they received a HTG clamp alone or once a simultaneous HTG and EH clamp was given. During the steady state, the average TG concentration (4.07 f 0.02 vs 3.98 * 0.07 mmol/l, ns., mean ? SEM) as well as the average infusion rate of lipids, i.e. the elimination rate of fat, (0.21 ? 0.02 vs 0.22 + 0.02 gTG/min, n.s.) were no different with and witout the EH clamp. The mean energy expenditure (2113 f 82 vs 1927 + 54 kcal/24 h, P < 0.01) and respiratory quotient (0.85 f 0.07 vs 0.79 f 0.01, P < 0.01) were higher but the FFA concentration was lower (0.40 + 0.05 vs 0.82 * 0.07 mmolll, P c 0.001) during the EH clamp. In conclusion, administration of glucose and insulin as an euglycaemic hyperinsulinaemic clamp decreases FFA levels but does not influence the plasma elimination rate of a fat emulsion. The data furthermore suggest that such an infusion is accompanied by an increased glucose oxidation and a virtually unaltered lipid utilisation.
P.3 Higher plasma elimination rate of MCT/LCT versus LCT emulsion in a hypertriglyceridemic (Zucker) strain of rat. F. Sultan’, D. Lagrange2, F. Benhizia* and S. Griglio*. ‘B. Braun Medical S.A., F-92107 Boulogne, *lNSERM F-75006 Paris, France.
U-177,
Introduction: The available fat emulsions for intravenous use are composed of long chain triglycerides (LCT) or, more recently, of a mixed MCT/LCT emulsion containing an equal proportion of medium chain triglycerides (MCT) and LCT. Lipid emulsion particles are quite similar to chylomicrons and are metabolised and cleared from the circulation by identical mechanisms [l]. In the course of TPN with conventional LCT emulsion, there is a high frequency of hypertriglyceridemia leading to a decrease in lipid intake and even more to a total withdrawal of the perfusion. The aim of the present work was to use a hypertriglycerfdemic strain of rat for comparing the elimination kinetics of both MCT/LCT and LCT emulsions. Materials and methods: After light diethyl ether anaesthesia, male obese Zucker rats (fa/fa) of 450 g were injected with 20 mg of TG of either MCT/LCT (MedialipideB 20%. 8. Braun Medical SA)
P.2 The effects of starvation and infused adrenaline on fatty acid turnover and oxidation in man. K. Weber’, J. Taylor’, D. Forster’, H. Greathead’, J. Dawson*, P. J. Butte4 and 1. A. Macdonald', ‘Department of Physiology and Pharmacology, Medical School, Queen’s Medical Centre, Nottingham and *School of Agriculture, University of Nottingham, Sutton Bonnington, UK. During starvation there is a progressive increase in plasma fatty acid concentrations with a concurrent rise in the use of fat as an 30
AND CARBOHYDRATE
P.1 Influence of an euglycaemic hyperinsulinaemic clamp on plasma elimination rate and utilisation of exogenous fat - determined by hypertriglyceridaemic clamp technique. A. Thiirne, J. Nordenstrtim and A. Alvestranti. Departments of Surgery and *Rena/ University Hospitaal, Sweden.
Medicine,
METABOLISM
energy source by the body. The purposes of the present study were to examine the relationship between plasma fatty acid turnover and oxidation after short periods of fasting and to see how adrenaline infusion affected these processes. Nine healthy subjects (mean age 22.9 f 1.2 (SE) years, body mass index 22.0 t 0.80 kg/m’) were recruited. Each attended after 12, 36 and 72 hrs of fasting, with the studies done in random order. Basal blood samples were taken for measurement of plasma palmitate concentration and (1 ,‘3C]-palmitate enrichment using mass spectrometry. Expired air was was sampled for analysis of 13C02 enrichment. A NaH13C0, bolus was given and a [l ,‘3C]-palmitate infusion commenced with blood and air samples obtained after 45min. Adrenaline was then infused at 2.5 ng min-’ kg ideal body weight-’ for 90 minutes, whilst the [1,‘3C]-palmitate was continued, with further samples taken at IO min intervals. Indirect calorimetry was performed throughout. Basal palmitate turnover increased with duration of fasting from 1.48 + 0.22 to 1.95 rt 0.34 to 2.26 I 0.33mmolmin-’ kg body weight-’ after 12, 36 and 72 hrs respectively (P < 0.01, ANOVA). Basal plasma palmitate oxidation also rose from 0.64+0.09 to 0.85 + 0.16 to 0.83&0.11 mmol min” kg body weight-’ (P < 0.05, ANOVA). The proportion of plasma palmitate turnover which was oxidised was unaffected by fasting (44 * 2, 46 f 5 and 42 ? 4% respectively). In response to adrenaline the peak plasma palmitate turnovers were 2.31 + 0.36, 2.79 f 0.67 and 2.97 + 0.73 mmol mini’ kg body weight-’ respectively, there being no significant effect of fasting on the magnitude of the response. By the end of the adrenaline infusion the percent of turnover which was oxidised had fallen to 34 f 3% (12 hrs), 36 + 4% (36 hrs) and 25 f 4% (72 hrs). In the basal state fasting leads to increased lipolysis and fat oxidation, However, fasting has no effect on the percent of plasma fatty acid turnover which is oxidised. Adrenaline infusion appears to favour intratissue lipid oxidation over plasma lipid oxidation. The oxidation of skeletal muscle fat stores may be responsible for skeletal muscle thermogenesis and the enhanced thermogenic response to adrenaline seen after fasting.
Huddinge
Previous studies have suggested that the plasma insulin concentration is the major determinant for the rate of lipolysis but it is less clear whether the insulin niveau is important for the plasma elimination rate of exogenous fat. The purpose of the present study was to examine the possible influence of glucose and insulin administration on the elimination rate and utilisation of a fat emulsion by using indirect calorimetry (IC), hypertriglyceridaemic (HTG) and euglycaemic hyperinsulinaemic (EH) clamp techniques. The HTG and EH clamps and the indirect calorimetry were performed as follows: A priming dose of a LCT emulsion 13 mg triglycerides (TG)/kg BW x min was given in order to reach a TG concentration of 4 mmol/l. The infusion rate was adjusted to maintain TG at 4 mmolll during 180 min. The infusion rate of lipids during the steady state (at 180 min) reflects the plasma elimination rate of exogenous fat. After a bolus dose insulin was administered simultaneously with the lipids by a constant infusion of 20mUtm’ BSA x min. The glucose level was maintained at 8 mmol/l during the steady state period by adjustment of the infusion rate of a 20% glucose solution. Continuous IC was carried out in the basal state and then throughout the study period. Ten healthy male volunteers with an average age of 30 years (24-44yrs) and a body mass index 24 (21-26) were randomly allocated for two treatment order groups in an open, cross-over study. The subjects were studied on two occasions, once they received a HTG clamp alone or once a simultaneous HTG and EH clamp was given. During the steady state, the average TG concentration (4.07 f 0.02 vs 3.98 * 0.07 mmol/l, ns., mean ? SEM) as well as the average infusion rate of lipids, i.e. the elimination rate of fat, (0.21 ? 0.02 vs 0.22 + 0.02 gTG/min, n.s.) were no different with and witout the EH clamp. The mean energy expenditure (2113 f 82 vs 1927 + 54 kcal/24 h, P < 0.01) and respiratory quotient (0.85 f 0.07 vs 0.79 f 0.01, P < 0.01) were higher but the FFA concentration was lower (0.40 + 0.05 vs 0.82 * 0.07 mmolll, P c 0.001) during the EH clamp. In conclusion, administration of glucose and insulin as an euglycaemic hyperinsulinaemic clamp decreases FFA levels but does not influence the plasma elimination rate of a fat emulsion. The data furthermore suggest that such an infusion is accompanied by an increased glucose oxidation and a virtually unaltered lipid utilisation.
P.3 Higher plasma elimination rate of MCT/LCT versus LCT emulsion in a hypertriglyceridemic (Zucker) strain of rat. F. Sultan’, D. Lagrange2, F. Benhizia* and S. Griglio*. ‘B. Braun Medical S.A., F-92107 Boulogne, *lNSERM F-75006 Paris, France.
U-177,
Introduction: The available fat emulsions for intravenous use are composed of long chain triglycerides (LCT) or, more recently, of a mixed MCT/LCT emulsion containing an equal proportion of medium chain triglycerides (MCT) and LCT. Lipid emulsion particles are quite similar to chylomicrons and are metabolised and cleared from the circulation by identical mechanisms [l]. In the course of TPN with conventional LCT emulsion, there is a high frequency of hypertriglyceridemia leading to a decrease in lipid intake and even more to a total withdrawal of the perfusion. The aim of the present work was to use a hypertriglycerfdemic strain of rat for comparing the elimination kinetics of both MCT/LCT and LCT emulsions. Materials and methods: After light diethyl ether anaesthesia, male obese Zucker rats (fa/fa) of 450 g were injected with 20 mg of TG of either MCT/LCT (MedialipideB 20%. 8. Braun Medical SA)
P.2 The effects of starvation and infused adrenaline on fatty acid turnover and oxidation in man. K. Weber’, J. Taylor’, D. Forster’, H. Greathead’, J. Dawson*, P. J. Butte4 and 1. A. Macdonald', ‘Department of Physiology and Pharmacology, Medical School, Queen’s Medical Centre, Nottingham and *School of Agriculture, University of Nottingham, Sutton Bonnington, UK. During starvation there is a progressive increase in plasma fatty acid concentrations with a concurrent rise in the use of fat as an 30