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The combined effects of exercise and food intake on adipose tissue and splanchnic metabolism
Abstract
Seven young, healthy male subjects were each studied in two separate experiments. (1) Subjects exercised for 60 min at 55% of peak oxygen consumption in the fasted state ending 30 min before a meal (60% of energy as carbohydrate, and 20% of energy as lipid and protein each) comprising 25% of the total daily energy intake, and were then studied for another 150 min postprandially during rest (E→M). (2) One hour after a similar meal, subjects exercised for 60 min and were then studied for another 180 min postexercise during rest (M→E). Regional adipose tissue and splanchnic tissue metabolism were measured by Fick's Principle. Food intake before exercise reduced whole-body lipid combustion during exercise to about 50% of the combustion rate found during exercise in the fasted state. The increase in subcutaneous, abdominal adipose tissue lipolysis during exercise was not influenced by preexercise food intake, while the fatty acid mobilization was increased by only 1.5-fold during postprandial exercise compared to a fourfold increase during exercise in the fasted state. During exercise, catecholamine concentrations increased similarly in the fasted and the postprandial state, while the insulin concentration was twofold higher postprandially. These results indicate that the increase in catecholamine concentrations during exercise is a more important determinant of the adipose tissue lipolytic rate than the decrease in insulin concentration. Furthermore, food intake either 30 min after or 1 h before exercise prevents the postexercise increase in adipose tissue glycerol and fatty acid release which normally takes place in fasting subjects at least up to 2.5 h postprandially. Postprandial exercise led to a faster increase in postprandial lipaemia. This could not be accounted for by changes in the regional splanchnic tissue or adipose tissue triacylglycerol metabolism. Exercise was able to increase hepatic glucose production irrespective of food intake before exercise. It is concluded that exercise performed in the fasted state shortly before a meal leads to a more favourable lipid metabolism during and after exercise than exercise performed shortly after a meal.
Adipose tissue and the liver provide lipid chemical energy to skeletal muscles during exercise as free fatty acids and triacylglycerol-rich lipoproteins (TRL). In previous studies on fasting subjects we have shown that lipolysis and the mobilization of fatty acids from subcutaneous, abdominal adipose tissue increases about threefold during prolonged bicycle exercise of moderate intensity. After an initial decrease, a pronounced increase in lipolysis and fatty acid mobilization lasting for at least 3 h during postexercise recovery also takes place (Mulla et al. 2000). The fatty acids that are mobilized in this period are only to a small extent taken up in the lower extremities (Mulla et al. 2000). The splanchnic tissues can, on the other hand, account for about 50% of the whole-body fatty acid disappearance in the postexercise recovery period and for about 60% of the whole-body fatty acid re-esterification. About half of the fatty acids which are taken up in the splanchnic tissues in a 3 h postexercise period are released again as triacylglycerol (TAG) in this period (Van Hall et al. 2002). Under the experimental conditions applied by Mulla et al. (Mulla et al. 2000) and van Hall et al. (Van Hall et al. 2002), the subjects were studied in the postabsorptive phase. This pronounced increase in lipolysis postexercise is not due to the prolonged fasting situation since we have previously shown that after an overnight fast the net release of glycerol and fatty acids from the subcutaneous, abdominal adipose tissue remained constant for 3.5 h (Lyngsøet al. 2002). Furthermore, Horowitz et al. (Horowitz et al. 1999) have shown that the net release of glycerol and fatty acids from the subcutaneous, abdominal adipose tissue only increased about 20 and 35%, respectively, from 14 to 22 h of fasting.
Previously, we have described the effect of glucose intake on the splanchnic metabolism during rest (Simonsen et al. 1995; Bülow et al. 1999). In those experiments we demonstrated that there is a close co-ordination between the adipose tissue fatty acid release and splanchnic fatty acid uptake, as well as between the splanchnic very-low-density lipoprotein (VLDL)-TAG output and adipose tissue clearance of VLDL-TAG. The balance between lipid deposition and lipid mobilization in adipose tissue and liver plays an important role in the overall regulation of the lipid metabolism, and it is well established that a disturbance of the regulation and co-ordination of regional lipid metabolism in adipose tissue and liver can lead to metabolic diseases, e.g. obesity and type 2 diabetes mellitus. Thus, an understanding of the mechanisms regulating and co-ordinating regional lipid metabolism in relation to everyday activities either promoting or inhibiting lipid mobilization or deposition, e.g. food intake and exercise, is important. The combined effects of food intake either briefly before exercise or briefly after exercise have never been examined with regard to regional adipose tissue and splanchnic tissue metabolism. Thus, the aim of the present experiments was to study the effect of exercise on regional adipose tissue and splanchnic tissue metabolism during exercise and postexercise recovery when exercise was either preceded or followed by a carbohydrate-rich mixed meal to test the hypothesis that the order of food intake and exercise will influence the metabolic response to exercise as well as during postexercise recovery.
Methods
Subjects
Seven young, healthy male subjects mean age (range) 25.1 years (21–31), mean weight 81.7 kg (68–101) and mean height 185.1 cm (180–191) were studied. Body composition was determined by dual energy X-ray absorptiometry (DEXA)-scanning as described in Experimental protocols. The average percentage body fat was 13% (8–26). The lean body mass was 66.7 kg (58–72) and the fat mass was 10.9 kg (6–25). Mean peak oxygen uptake was 4224 ml min−1 (3200–5100). The subjects were given a written and an oral description of the study and the possible risks and discomfort involved before giving their voluntary consent to participate. The study was performed according to the ‘Declaration of Helsinki II’ and was approved by the Ethical Committee of Copenhagen, Denmark (project no. 01-039/02).
Experimental protocols
Subjects participated in two experiments, with about 3 weeks between experiments. These experiments consisted of one experiment in which the subjects exercised for 60 min in the fasted state ending 30 min before the meal and the subjects were then studied for another 150 min postprandially during rest (E→M). In a second experiment, the subjects exercised for 60 min commencing 60 min after the food intake, and the experiment was continued for another 180 min during rest (M→E). The test order of the two experiments was randomized to give a balanced design.
Prior to the experiments, the maximum oxygen uptake (V̇O2,max) of the subjects was determined. They exercised in the semirecumbent position on an electrically braked cycle ergometer (ergometrics er900L, ergoline, Bitz, Germany), initially at 50 W, and then, essentially, at a 50 W increase in load every 2 min until exhaustion. Oxygen uptake and carbon dioxide output were measured continuously during the test by means of an Oxycon Champion system (Jaeger, Wuerzburg, Germany), using facemask and breath-to-breath techniques. On the same day, body composition was determined by DEXA-scanning (Lunar DPX-IQ, software version 4.6c, Lunar Corporation, Madison, WI, USA), using the medium scan mode and extended research analysis.
Habitual dietary intake was recorded for 2 days before the first experiment and replicated before the subsequent experiment. The subjects refrained from vigorous physical activity 24 h prior to the experiments. The experiments were initiated at 8.00 a.m. when the subjects arrived in the laboratory after a 12 h overnight fast.
Main experiments
Figure 1 outlines the design of the study. In both experiments, the subjects exercised for 60 min at 55% of their V̇O2,max, and the meal comprised an omelette with tomatoes, white bread, cottage cheese, marmalade and orange juice (121 ± 8 g carbohydrate (60% of energy), 20 ± 1 g fat (20% of energy), and 38 ± 3 g protein (20% of energy), in total 3.5 ± 0.2 MJ energy), providing 25% of each participant's reported total daily dietary intake (14.77 ± 0.43 MJ energy), which was calculated using a database (Dankost, Danish Catering Centre, Copenhagen, Denmark). Each meal was supplemented with 1.5 g of soluble paracetamol dissolved in 150 ml of water; postprandial changes in the blood concentration of paracetamol can be used as an indirect measure of the gastric emptying rate (Rawlins et al. 1977; Clements et al. 1978; Tarling et al. 1997).
Catheterizations
The subjects were catheterized in a subcutaneous vein on the anterior abdominal wall, in a hepatic vein, and in a radial artery. The subcutaneous, abdominal vein was catheterized as previously described (Simonsen et al. 1994) during ultrasound/colour-Doppler imaging of the vein. A 22 g 10 cm polyurethane catheter (Ohmeda, Swindon, UK) was inserted using the Seldinger technique. After insertion, the catheter was kept patent throughout the experiment by continuous infusion of isotonic sodium chloride at a rate of 40 ml h−1. The right femoral vein was catheterized during local anaesthesia (lidocaine 1%, 5–10 ml) and a polyethylene catheter (outer diameter 2.0 mm) was advanced to a right-sided hepatic vein and left in situ with the tip positioned 1–2 cm from the wedge position during the rest of the experiment. The catheterization was performed during fluoroscopic control. This catheter was kept patent throughout the experiment by continuous infusion of isotonic sodium chloride at a rate of 40 ml h−1. Another catheter was inserted percutaneously into the radial artery of the nondominant arm during local anaesthesia (1 ml 1% lidocaine) with an Artflon (Ohmeda, Swindon, UK). The catheter was kept patent with regular flushing with isotonic sodium chloride.
Measurements
Adipose tissue blood flow
Adipose tissue blood flow was determined by washout of 133xenon, which was injected in gaseous form in the tissue. This new labelling technique has recently been evaluated and described in our laboratory (Simonsen et al. 2003). About 1 MBq gaseous 133xenon mixed in about 0.1 ml of atmospheric air was injected into the subcutaneous adipose tissue contralateral to the catheter position. The washout rate of 133xenon was measured continuously by a scintillation counter system strapped to the skin surface above the 133xenon depot (Oakfield Instruments, Oxford, UK). The adipose tissue blood flow was calculated from the mean washout rate constant determined in 20 min periods coinciding with the time of blood sampling (10 min before and after blood sampling), except during exercise where the mean washout rate constant was determined in the last 15 min. A tissue/blood partition coefficient for xenon of 8 ml g−1 was used (Bülow et al. 1987).
Splanchnic blood flow
Splanchnic blood flow was measured by continuous infusion of indocyanine green (ICG) (Henriksen & Winkler, 1987). Immediately after the catheterization, a priming dose (1 mg) of ICG was given, followed by a continuous infusion (167 μg h−1) for the rest of the experiment. After 60 min of infusion, a steady arterial concentration is normally achieved. The resting period was then begun, unless steady state in other aspects (e.g. steady adipose tissue blood flow, stable whole-body oxygen consumption) was not reached.
Blood sampling
Blood samples were preferably drawn simultaneously from the three catheters. During exercise, blood samples were supposed to be drawn at 45 and 60 min after commencement of exercise. However, in some experiments it was impossible to draw two sample sets due to technical difficulties (e.g. kinking catheters or collapsed veins) and that is why all parameters measured during exercise are given as means in order to reduce the variability of the data sets. Since regional metabolic steady state has usually been reached after 45 min of moderate-intensity exercise, this problem does not affect the general pattern emerging from the data sets (Mulla et al. 2000; Lange et al. 2002; Van Hall et al. 2002). Blood was collected from all three catheters for measurements of glycerol, fatty acids, total TAG, chylomicron- and VLDL-TAG, glucose and lactate. Blood was drawn from the arterial and the hepatic venous catheters for determination of oxygen concentration. In addition, blood was collected from the artery for measurements of insulin, catecholamines and paracetamol. The blood was collected in vials at 4°C, and whole blood was immediately deproteinized or the plasma was separated by centrifugation at 4°C. The samples were then stored at −20°C until analysis, except samples for fatty acid and hormone analysis which were stored at −80°C, and samples for chylomicron- and VLDL-TAG analysis which were kept at 4°C until the next day, when separation by ultracentrifugation took place. The blood for determination of oxygen concentration was drawn anaerobically in heparinized syringes and immediately analysed.
Blood analysis
Glycerol, glucose, and lactate were measured in perchloric acid extracts of whole blood, and fatty acids and TAG were measured in EDTA plasma with enzymatic methods as previously described (Humphreys et al. 1990; Bülow et al. 1999). Chylomicrons and VLDL were separated by ultracentrifugation (Potts et al. 1994; Bülow et al. 1999). Approximately 1.5 ml of plasma was layered under a solution of density 1.006 g ml−1 in preweighed Beckman 6 ml polyallomer bell-top tubes. The tubes were re-weighed and the volume of plasma was obtained by difference. The tubes were heat sealed and ultracentrifuged for 30 min at 26 000 r.p.m. in the outer ring of a 44-place Kontron TFT45.6 rotor, giving on average 58 450 g. The chylomicrons were obtained by removing the top layer (1.5 ml) of the tube in a tube-slicer. For isolation of VLDL, the total chylomicron infranate volume (4.5 ml) was then transferred to a Beckman 6 ml polyallomer Bell-top tube, and the necessary additional fluid volume, with density 1.006 g ml−1, was added to fill the tube. The tubes were heat sealed and ultracentrifuged for 20 h at 40 700 r.p.m. in a 44-place Kontron TFT45.6 rotor in two concentric rings, inner ring 145 000 g (average), outer ring 182 000 g (average). A 3.5 ml volume of the top layer was removed for VLDL analysis. All fractions were weighed to estimate their volume and thus to allow for calculation of the corresponding concentrations of chylomicron- and VLDL-TAG in the original plasma. Chylomicron- and VLDL-TAG were determined as previously described (Humphreys et al. 1990). Paracetamol concentrations in EDTA plasma were measured using high performance liquid chromatography (HPLC) with electrochemical detection (Whelpton et al. 1993; Tarling et al. 1997). Insulin concentrations in arterial EDTA plasma were determined using a commercial radioimmunoassay (RIA) kit (NOVO Nordic, Bagsvaerd, Denmark). Catecholamines were determined in EGTA–glutathione stabilized plasma by HPLC with electrochemical detection (Forster & Macdonald, 1999). Oxygen concentrations were determined in an ABL 725 (Radiometer Copenhagen, Copenhagen, Denmark). The plasma ICG concentration was determined in heparinized plasma by spectrophotometry at 805 and 904 nm. In order to enable correction for any quasi-steady state in the arterial concentration of ICG, a mean of three samples drawn within 10 min was used.
Whole-body measurements
Whole-body oxygen consumption and respiratory exchange ratio (RER) were measured by ventilated hood system in the resting periods and by facemask and breath-by-breath technique during exercise. Heart rate and intra-arterial blood pressure were monitored continuously during the experiment via an Athena (S & W, Copenhagen, Denmark) interfaced to the Oxycon Champion system.
Calculations
Splanchnic blood flow and subcutaneous adipose tissue blood flow were calculated as previously described (Bülow, 1983; Simonsen et al. 1995). Splanchnic and subcutaneous adipose tissue metabolite net fluxes were calculated by multiplication of the arterial–venous or venous–arterial concentration difference of the metabolite and the appropriate flow value (whole blood for calculation of glycerol, glucose and oxygen fluxes, and plasma flow for calculation of fatty acid and TAG fluxes). Adipose tissue lipolytic rate was taken to be equal to the adipose tissue net release of glycerol when this is adjusted from the amount of glycerol originating from the clearance of TAG across the adipose tissue. This is an approximation, since we have previously shown that there is a small reuptake of glycerol in adipose tissue (Van Hall et al. 2002). However, for practical purposes this approximation does not significantly affect the calculations of fatty acid/glycerol release ratios and fatty acid re-esterification rates. The adipose tissue fatty acid re-esterification rate was taken to be the difference between the expected fatty acid release (three times the net glycerol release) and the measured actual net fatty acid release.
Whole-body lipid oxidation rates were calculated from the whole-body oxygen consumption and carbon dioxide production corrected for an average protein combustion rate (100 μg kg−1 min−1) (Simonsen et al. 1993) using conventional principles for indirect calorimetry as described by Frayn (Frayn, 1983).
Splanchnic delivery of fatty acids was calculated as the arterial concentration multiplied by the splanchnic plasma flow.
Statistics
Data were analysed using SPSS for Windows Release 11.5 (SPSS Inc., Chicago, IL, USA). All data are presented as means ± s.e.m. or mean (range). ANOVA and subsequent paired t test was used for analysis of changes with time in whole-body parameters, blood/plasma flows, and tissue substrate fluxes between the experiments. A paired t test was used for analysis of differences between experiments. Postprandial areas under curves were calculated as changes from baseline by the trapezoid method for net substrate fluxes across adipose and splanchnic tissues. Differences between experiments were analysed using a paired t test. P < 0.05 was considered statistically significant.
Results
Whole body
The mean oxygen uptake, RERs and calculated lipid oxidation rates before, during and after exercise are given in Table 1. Oxygen uptake during exercise was the same in the two experiments. During postprandial exercise (M→E), RER was significantly higher, and accordingly, whole-body lipid oxidation rate was significantly lower compared with exercise performed in the fasted state (E→M).
Table 1
Whole-body oxygen uptake, respiratory exchange ratio (RER), and lipid oxidation rates
| No of mins | −60 | −15 | 0 | Exercise | 90 | 120 | 150 | 180 | 210 | 240 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Oxygen uptake | M→E | 280 ± 15* | 311 ± 14† | 310 ± 14† | 2231 ± 113† | 328 ± 18† | 320 ± 17† | 312 ± 17† | 309 ± 18† | 308 ± 17 | 298 ± 19 |
| (ml min−1) | E→M | 268 ± 15 | 268 ± 15 | 268 ± 15 | 2249 ± 119† | 327 ± 26*† | 340 ± 23† | 340 ± 23† | 310 ± 21† | 333 ± 13† | 334 ± 13† |
| RER | M→E | 0.86 ± 0.03* | 0.91 ± 0.03† | 0.90 ± 0.03† | 0.91 ± 0.01†‡ | 0.88 ± 0.02 | 0.88 ± 0.03 | 0.85 ± 0.03 | 0.86 ± 0.04 | 0.82 ± 0.02 | 0.81 ± 0.03† |
| E→M | 0.84 ± 0.01 | 0.84 ± 0.01 | 0.84 ± 0.01 | 0.83 ± 0.01 | 0.80 ± 0.05* | 0.85 ± 0.01 | 0.85 ± 0.01 | 0.86 ± 0.01 | 0.83 ± 0.01 | 0.83 ± 0.01 | |
| Lipid oxidation rate | M→E | 0.07 ± 0.02* | 0.05 ± 0.02 | 0.05 ± 0.02 | 0.35 ± 0.03†‡ | 0.07 ± 0.01 | 0.07 ± 0.02 | 0.08 ± 0.02 | 0.07 ± 0.02 | 0.09 ± 0.01† | 0.10 ± 0.02 |
| (g min−1) | E→M | 0.07 ± 0.00 | 0.07 ± 0.00 | 0.07 ± 0.00 | 0.65 ± 0.07† | 0.06 ± 0.04* | 0.09 ± 0.01 | 0.09 ± 0.01 | 0.07 ± 0.01 | 0.09 ± 0.01† | 0.09 ± 0.01† |
Values are means ± s.e.m.
M→E, postprandial exercise experiment; E→M, preprandial exercise experiment.
Arterial metabolite and hormone concentrations
The arterial concentrations of the metabolites and hormones before, during and after exercise are given in Tables 2 and and3.3. The concentrations of glycerol and fatty acids increased during exercise and decreased just after the meal in both experiments. Immediately postexercise, the glycerol concentrations decreased to preexercise levels, and, when the meal was ingested postexercise (E→M), this decrease was maintained throughout the experiment. In contrast, towards the end of the experiment when food was ingested prior to the exercise bout (M→E), the glycerol concentration increased again to the level reached during exercise. This postexercise pattern was the same regarding the fatty acid concentration, except that it increased to a level about fourfold higher than during exercise.
Table 2
Arterial concentrations of metabolites
| No of mins | −60 | −15 | 0 | Exercise | 90 | 120 | 150 | 180 | 210 | 240 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Glycerol | M→E | 38 ± 7* | 19 ± 3† | 17 ± 4† | 62 ± 7†‡ | 21 ± 3†‡ | 27 ± 5† | 47 ± 10‡ | 45 ± 6‡ | 66 ± 10†‡ | 64 ± 8†‡ |
| (μmol l−1) | E→M | 48 ± 3 | 47 ± 4 | 48 ± 4 | 200 ± 29† | 57 ± 6* | 31 ± 6 | 20 ± 3† | 20 ± 4† | 32 ± 12 | 24 ± 6† |
| Fatty acids | M→E | 359 ± 59* | 71 ± 9† | 40 ± 5†‡ | 158 ± 34†‡ | 85 ± 9†‡ | 141 ± 21†‡ | 312 ± 83‡ | 375 ± 86‡ | 538 ± 132‡ | 625 ± 106†‡ |
| (μmol l−1) | E→M | 406 ± 52 | 454 ± 64 | 439 ± 52 | 660 ± 135† | 674 ± 110*† | 294 ± 59 | 76 ± 19† | 83 ± 42† | 178 ± 130 | 162 ± 60 |
| Total TAG | M→E | 791 ± 93* | 784 ± 93 | 797 ± 95 | 1023 ± 168†‡ | 937 ± 96‡ | 1014 ± 113†‡ | 1012 ± 115†‡ | 1030 ± 121†‡ | 903 ± 112 | 906 ± 126 |
| (μmol l−1) | E→M | 625 ± 58 | 628 ± 66 | 597 ± 50 | 634 ± 49 | 561 ± 58* | 574 ± 58 | 622 ± 71 | 613 ± 71 | 674 ± 78 | 790 ± 90† |
| Chylomicron-TAG | M→E | 102 ± 21* | 100 ± 19 | 102 ± 21 | 135 ± 30†‡ | 174 ± 31†‡ | 200 ± 38†‡ | 194 ± 50†‡ | 239 ± 61†‡ | 150 ± 33 | 149 ± 37 |
| (μmol l−1) | E→M | 75 ± 15 | 60 ± 11 | 56 ± 10 | 58 ± 7 | 53 ± 6* | 67 ± 13 | 66 ± 18 | 65 ± 16 | 101 ± 19† | 162 ± 35† |
| VLDL-TAG | M→E | 336 ± 54* | 431 ± 78 | 378 ± 66 | 439 ± 81†‡ | 438 ± 75†‡ | 459 ± 76†‡ | 475 ± 71†‡ | 432 ± 60†‡ | 393 ± 68 | 398 ± 77 |
| (μmol l−1) | E→M | 238 ± 37 | 249 ± 38 | 255 ± 39 | 246 ± 38 | 226 ± 33* | 234 ± 41 | 243 ± 50 | 273 ± 60 | 267 ± 59 | 285 ± 53 |
| 3-OHB | M→E | 63 ± 11* | 28 ± 2† | 24 ± 2†‡ | 36 ± 2‡ | 35 ± 3†‡ | 30 ± 2†‡ | 45 ± 6 | 73 ± 17 | 129 ± 41‡ | 177 ± 68†‡ |
| (μmol l−1) | E→M | 72 ± 14 | 86 ± 22 | 88 ± 28 | 112 ± 30 | 266 ± 77*† | 99 ± 33 | 37 ± 5 | 31 ± 3 | 59 ± 34 | 52 ± 23 |
| Glucose | M→E | 5.20 ± 0.10* | 7.65 ± 0.56†‡ | 6.48 ± 0.54†‡ | 4.96 ± 0.15 | 5.55 ± 0.19‡ | 5.34 ± 0.16‡ | 5.43 ± 0.10‡ | 5.40 ± 0.15 | 5.42 ± 0.20 | 5.18 ± 0.17 |
| (mmol l−1) | E→M | 5.07 ± 0.08 | 5.05 ± 0.08 | 5.04 ± 0.06 | 4.71 ± 0.15 | 4.84 ± 0.258* | 6.91 ± 0.61† | 7.30 ± 0.41† | 6.09 ± 0.37 | 5.53 ± 0.27 | 5.51 ± 0.25 |
Values are means ± s.e.m. TAG, triacylglycerol; VLDL, very-low-density lipoprotein; 3-OHB, 3-hydroxybutyrate.
Table 3
Arterial concentrations of hormones
| No of mins | −60 | −15 | 0 | Exercise | 90 | 120 | 150 | 180 | 210 | 240 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Insulin | M→E | 24 ± 5* | 300 ± 58†‡ | 222 ± 48†‡ | 40 ± 8†‡ | 72 ± 13‡ | 47 ± 10‡ | 30 ± 4‡ | 32 ± 4‡ | 20 ± 3‡ | 16 ± 5‡ |
| (pmol l−1) | E→M | 22 ± 3 | 21 ± 2 | 22 ± 4 | 19 ± 5 | 24 ± 6* | 231 ± 35† | 214 ± 17† | 130 ± 21† | 69 ± 16† | 76 ± 13† |
| Noradrenaline | M→E | 0.65 ± 0.08* | 0.78 ± 0.09 | 0.75 ± 0.10 | 3.95 ± 0.71† | 0.60 ± 0.08 | 0.72 ± 0.13 | 0.62 ± 0.08 | 0.61 ± 0.09 | 0.54 ± 0.07 | 0.60 ± 0.12 |
| (nmol l−1) | E→M | 0.70 ± 0.12 | 0.62 ± 0.08 | 0.63 ± 0.10 | 4.53 ± 0.86† | 0.74 ± 0.09* | 1.01 ± 0.21 | 0.90 ± 0.15 | 0.86 ± 0.13 | 0.79 ± 0.10 | 0.80 ± 0.14 |
| Adrenaline | M→E | 0.23 ± 0.05* | 0.11 ± 0.03† | 0.15 ± 0.04 | 0.51 ± 0.12† | 0.13 ± 0.03‡ | 0.22 ± 0.06 | 0.27 ± 0.07 | 0.37 ± 0.10 | 0.36 ± 0.09 | 0.44 ± 0.12†‡ |
| (nmol l−1) | E→M | 0.16 ± 0.03 | 0.17 ± 0.04 | 0.18 ± 0.03 | 0.73 ± 0.15† | 0.26 ± 0.04* | 0.15 ± 0.03 | 0.12 ± 0.03 | 0.18 ± 0.05 | 0.21 ± 0.04 | 0.17 ± 0.03 |
Values are mean ± s.e.m.
In both experiments, the arterial TAG concentrations increased with time. However, when exercise was preceded by food intake (M→E), the TAG concentration was increased significantly already during exercise as opposed to the preprandial exercise experiment (E→M) in which the TAG concentration first began to increase 180 min postexercise (Table 2): the average integrated increase was significantly higher compared with the other experiment (E→M) (141 ± 27 versus −9 ± 10 μmol l−1 min−1). Arterial chylomicron-TAG concentrations increased significantly above fasting levels about 120 min after the meal in both experiments (Table 2). The VLDL-TAG increased significantly during and after exercise when it was performed postprandially (M→E) (Table 2): the average integrated increase was higher compared to the other experiment (E→M) (38 ± 13 versus 12 ± 15 μmol l−1 min−1, P = 0.09).
In the preprandial exercise experiment (E→M), 3-hydroxybutyrate (3-OHB) increased significantly 30 min postexercise just before meal intake. This was in contrast to the postprandial exercise experiment (M→E) where 3-OHB decreased after the meal and did not increase again until 150 min postexercise. In both experiments the glucose concentrations increased after the meal.
The insulin concentrations (Table 3) peaked within the first hour after the meal and then decreased steadily in both experiments. During exercise, the insulin concentration was significantly higher when exercise was preceded by a meal (M→E) compared to the fasted state (E→M). The catecholamine concentrations increased to equal levels during exercise in the fasted and the postprandial states. Towards the end of the postprandial exercise experiment (M→E), the adrenaline concentration increased significantly.
In both experiments, the arterial paracetamol concentrations peaked 15 min after administration and then began to decrease. At no time did arterial paracetamol concentration differ between experiments (Fig. 2).
Adipose tissue metabolism
Figure 3 shows the subcutaneous, abdominal adipose tissue blood flow before, during and after exercise. There was a significant increase during exercise performed in the fasted state (E→M). When food was ingested prior to the exercise bout (M→E), the adipose tissue blood flow increased after the meal and did not increase further during exercise. In both experiments, blood flow decreased to the basal level immediately postexercise. In the preprandial exercise experiment (E→M) it increased again towards the level reached during exercise at 90 min after the meal, whereas in the postprandial exercise experiment (M→E), there was an increase postexercise by the end of the experiment.
The arrow indicates commencement of food ingestion. Values are means ± s.e.m. *P < 0.05, significance of difference from baseline.
Figure 4 shows the time courses of the glycerol and fatty acid release rates from adipose tissue and TAG clearance by adipose tissue, as well as the adipose tissue fatty acid/glycerol release ratios. Glycerol outputs increased similarly during exercise in the two experiments, and the integrated glycerol output during exercise was 21 ± 9 and 28 ± 8 μmol (100 g)−1 (60 min)−1 when food was ingested before (M→E) and after exercise (E→M), respectively. However, the preexercise glycerol output was significantly lower when the exercise bout was preceded by food intake (M→E) compared with the fasting situation (E→M). In the postprandial exercise experiment (M→E), the glycerol output decreased initially postexercise, but it began to increase again, and by the end of the experiment it was increased compared to the baseline level and significantly higher than the glycerol output in the preprandial exercise experiment (E→M), in which the initial postexercise decrease was maintained throughout the experiment.
The arrow indicates commencement of food ingestion. Values are means ± s.e.m. *P < 0.05, significance of difference from baseline. #P < 0.05, significance of difference between experiments.
Overall, the fatty acid outputs mirrored the corresponding glycerol outputs, except during exercise. In the fasted state the fatty acid/glycerol ratio was about 2.6 and not significantly different between experiments. In both experiments, within 60 min postprandially, the ratio decreased to levels close to zero. During exercise the ratio was unchanged about 2.6 when exercise was performed preprandially (E→M), while it was only about 1.7 when exercise was performed postprandially (M→E). This difference was due to a fourfold increase in fatty acid mobilization during exercise in the fasted state compared to only a 1.5-fold increase during postprandial exercise (compared to baseline values). Immediately postexercise, the fatty acid/glycerol ratio increased to a maximum of about 4.7 in the fasted state (E→M), whereas this postexercise increase did not occur until 150 min after cessation of exercise, when exercise was performed postprandially (M→E).
TAG clearance was the same in both experiments and it was not possible to demonstrate a significant change from baseline after the meal in any of the experiments (the integrated mean TAG clearance was 59 ± 29 and 23 ± 40 nmol (100 g)−1 min−1 when food was ingested before and after exercise, respectively, P = 0.49). Similarly, it was not possible to show any significant changes in the net fluxes of VLDL- and chylomicron-TAG in either of the experiments (data not shown). With respect to glucose metabolism, it was not possible to show a significant increase in adipose tissue glucose uptake during either of the experiments and neither did it differ between the experiments (data not shown).
Splanchnic metabolism
During exercise blood flow was significantly increased when exercise was performed postprandially (M→E), while it was unchanged when performed in the fasted state (E→M). In both experiments, blood flow increased within the first 30–45 min after the meal and then began to decrease again (Table 4).
Table 4
Splanchnic blood flow and net substrate fluxes
| No of mins | −60 | −15 | 0 | Exercise | 90 | 120 | 150 | 180 | 210 | 240 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Blood flow | M→E | 1571 ± 117* | 2099 ± 127† | 2092 ± 155†‡ | 1903 ± 108‡ | 1999 ± 103 | 1968 ± 177‡ | 1872 ± 145 | 1670 ± 142‡ | 1948 ± 164 | 1774 ± 61 |
| (ml min−1) | E→M | 1541 ± 115 | 1546 ± 120 | 1537 ± 115 | 1431 ± 117 | 2102 ± 247* | 2600 ± 194† | 2293 ± 219† | 2188 ± 126† | 2220 ± 281 | 2202 ± 233 |
| Fatty acid delivery | M→E | 335 ± 65* | 89 ± 13†‡ | 50 ± 6†‡ | 197 ± 48‡ | 104 ± 12†‡ | 169 ± 29‡ | 355 ± 102‡ | 408 ± 104‡ | 644 ± 174† | 687 ± 112†‡ |
| (μmol min−1) | E→M | 364 ± 48 | 407 ± 58 | 399 ± 52 | 505 ± 147 | 887 ± 263*† | 530 ± 140 | 129 ± 49† | 128 ± 73† | 263 ± 192 | 273 ± 128 |
| Fatty acid uptake | M→E | 111 ± 27* | 10 ± 6† | −1 ± 7†‡ | −3 ± 12†‡ | −18 ± 24†‡ | 41 ± 18 | 98 ± 43‡ | 110 ± 38‡ | 152 ± 61 | 158 ± 39‡ |
| (μmol min−1) | E→M | 110 ± 14 | 129 ± 25 | 105 ± 15 | 112 ± 55 | 206 ± 52* | 85 ± 20 | 9 ± 8† | 25 ± 13† | 40 ± 38 | 52 ± 16† |
| 3-OHB output | M→E | 59 ± 19* | 10 ± 5† | 10 ± 5†‡ | 36 ± 6 | 18 ± 2 | 21 ± 6 | 64 ± 30 | 88 ± 45 | 112 ± 53 | 176 ± 49‡ |
| (μmol min−1) | E→M | 52 ± 12 | 83 ± 32 | 74 ± 26 | 201 ± 92 | 162 ± 72* | 2 ± 18 | −1 ± 6† | 8 ± 7 | 43 ± 33 | 9 ± 3† |
| Glucose output | M→E | 0.97 ± 0.13* | 3.15 ± 0.53†‡ | 2.48 ± 0.39†‡ | 4.08 ± 0.59† | 2.12 ± 0.40 | 1.03 ± 0.32‡ | 0.82 ± 0.27‡ | 1.12 ± 0.18‡ | −0.08 ± 0.34 | 0.94 ± 0.16 |
| (mmol min−1) | E→M | 0.86 ± 0.14 | 1.02 ± 0.10 | 0.74 ± 0.09 | 2.96 ± 0.35† | 0.75 ± 0.33* | 3.01 ± 0.40† | 2.20 ± 0.35 | 2.17 ± 0.38 | 2.32 ± 0.84 | 0.93 ± 0.36 |
| Oxygen uptake | M→E | 2.8 ± 0.2* | 3.8 ± 0.2† | 3.5 ± 0.2‡ | 6.5 ± 0.7† | 4.3 ± 0.2† | 3.7 ± 0.2† | 3.9 ± 0.2† | 3.8 ± 0.3† | 3.6 ± 0.3 | 3.7 ± 0.3 |
| (mmol min−1) | E→M | 2.8 ± 0.1 | 2.8 ± 0.2 | 2.7 ± 0.2 | 5.5 ± 0.8† | 4.0 ± 0.4*† | 4.2 ± 0.3† | 3.9 ± 0.2† | 4.1 ± 0.3† | 4.2 ± 0.5† | 4.5 ± 0.5† |
| Total TAG output | M→E | 11 ± 8* | 35 ± 10 | −9 ± 13 | −96 ± 58† | 8 ± 20 | −39 ± 35 | 14 ± 13 | 3 ± 10 | 1 ± 17 | −15 ± 32 |
| (μmol min−1) | E→M | 4 ± 14 | 2 ± 23 | 4 ± 8 | −11 ± 13 | 2 ± 13* | 39 ± 28 | 11 ± 10 | 10 ± 25 | 18 ± 17 | −23 ± 26 |
Values are means ± s.e.m.
When exercise was performed postprandially (M→E), the splanchnic fatty acid delivery decreased immediately after the meal, but during exercise it increased about fourfold (P < 0.05) (Table 4). In the other experiment (E→M), the splanchnic fatty acid delivery was unchanged during exercise but increased significantly above baseline at 30 min postexercise. The splanchnic fatty acid uptake mirrored the delivery except during exercise when the fatty acid uptake decreased to zero in the postprandial exercise experiment (M→E) despite the delivery being reduced by only about 40% compared to the fasted state (Table 4). The splanchnic 3-OHB output generally mirrored the fatty acid uptake, except that the 3-OHB output tended to be increased (P = 0.11) during exercise in the preprandial exercise experiment (E→M). In addition, while the fatty acid delivery and the 3-OHB output increased significantly above the preexercise fasting level towards the end of the postprandial exercise experiment (M→E), the uptake of fatty acids remained unchanged.
The glucose output increased significantly after food ingestion and during exercise in both experiments (Table 4). During exercise, oxygen uptake increased in both experiments, with a trend for a larger response when exercise was performed postprandially (M→E) compared with exercise performed in the fasted state (E→M) (P = 0.06) (Table 4). Furthermore, food intake per se led to an increase in splanchnic oxygen consumption. Postexercise, the splanchnic oxygen uptake did not differ between experiments.
In the postprandial exercise experiment (M→E), the total TAG output changed significantly to an uptake during exercise (Table 4). At no other time, in any of the experiments, could total TAG or VLDL-TAG (data not shown) be demonstrated to differ from baseline.
Discussion
The present experiments show that intake of a carbohydrate-rich meal 60 min before exercise of moderate intensity (M→E) reduces the whole-body lipid combustion rate to about 50% of the rate found during exercise in the fasted state (E→M). This is in accordance with what has been demonstrated in previous studies when glucose was supplied during exercise (Montain et al. 1991; Horowitz et al. 1997). However, the novel finding in this context is that the reduction in lipid combustion takes place simultaneously with an increase in anterior, abdominal subcutaneous adipose tissue lipolytic rate, which is comparable to the increase during exercise in the fasted state. This response to exercise happens irrespective of rather different circulating insulin concentrations in the two situations. The insulin concentration was about twofold higher during postprandial exercise (M→E) compared to exercise in the fasted state (E→M). However, the catecholamine response during exercise was the same whether exercise was performed in the fasted or in the postprandial state. This indicates that the increase in catecholamine concentration during exercise is a more important determinant of the adipose tissue lipolytic rate than the decrease in insulin concentration. Accordingly, the catecholamine stimulation of lipolysis overrides the insulin inhibition. Interestingly, a somewhat similar pattern has recently been described in adipose tissue where lipolysis induced by sympathetic stimulation via lower body negative pressure overrides the antilipolytic effect of an insulin infusion (Navegantes et al. 2003). On the other hand, the fatty acid mobilization during postprandial exercise (M→E) was reduced compared to the mobilization during exercise in the fasted state (E→M). This to a certain degree resembles the metabolic pattern we have recently described in adipose tissue in patients with insulin resistance and type 2 diabetes mellitus, in whom we also found that the fatty acid mobilization becomes restricted during exercise (Simonsen et al. 2004).
The reduction in whole-body lipid combustion found during postprandial exercise (M→E) could be due to reduced fatty acid availability as a consequence of reduced fatty acid mobilization from adipose tissue, and/or it could be due to increased glucose availability postprandially. It is likely that the latter mechanism is the most important since the arterial fatty acid concentration increased during postprandial exercise (M→E), although, it was about fourfold lower compared with the preprandial exercise situation (E→M). In essence, the metabolism in adipose tissue during exercise after food intake differs from the metabolism during exercise in the fasted state by having a higher intracellular fatty acid re-esterification rate both in relative and absolute terms.
A fatty acid/glycerol release ratio of 3.0 should be expected if all the fatty acids and glycerol created by lipolysis are released from the subcutaneous, abdominal adipose tissue. However, preexercise as well as during exercise, a release ratio of about 2.5–2.8 is normally found in the fasted state (Mulla et al. 2000; Van Hall et al. 2002). Furthermore, it has been suggested that some of the fatty acids, which are liberated by lipolysis in the adipose tissue during exercise, are not re-esterified but trapped intracellularly to be released early postexercise (Hodgetts et al. 1991). This may explain why the fatty acid/glycerol release ratio exceeds 3.0 about 30 min postexercise when the glycerol release decreases rapidly (Mulla et al. 2000; Van Hall et al. 2002). When exercise was preceded by food intake (M→E), this delayed fatty acid release did not seem to take place (Fig. 4D). Thus, the low fatty acid/glycerol release ratio found during and for 2 h postexercise in this situation is probably due to a high fatty acid re-esterification rate within the adipocytes rather than to trapping of fatty acids. Although it was not possible to show a significant increase in adipose tissue glucose uptake, probably due to the very small arteriovenous concentration differences for glucose, it is likely that increased glucose availability after the meal in combination with a relatively high insulin concentration resulted in the enhanced re-esterification in adipose tissue (Frayn et al. 1995), although the exact mechanisms which regulate fatty acid re-esterification have not been described in detail. It has previously been suggested that the reduction in lipid combustion during exercise is due to a reduction in lipolysis leading to a low fatty acid availability, which in turn will limit fatty acid oxidation in skeletal muscle (Horowitz et al. 1997). However, the present experiments show that the increase in regional subcutaneous, abdominal adipose tissue lipolysis is the same irrespective of whether exercise is performed in the fasted state or early postprandially. Thus, according to the present findings, the reduced fatty acid availability is due to the high fatty acid re-esterification in adipose tissue.
It is well documented that adipose tissue blood flow increases during exercise (Bülow & Madsen, 1978; Bülow & Tøndevold, 1982) and postprandially (Simonsen et al. 1990; Summers et al. 2001). However, the present experiments show that the circulatory effects of food and exercise are not additive, since the adipose tissue blood flow did not increase further during exercise in the postprandial exercise experiment (M→E).
We have previously shown that when exercise is performed in the fasted state, a pronounced increase in adipose tissue glycerol and fatty acid release take place in the postexercise recovery period beginning about 60 min after exercise (Mulla et al. 2000; Van Hall et al. 2002). This postexercise lipolytic response disappears when a carbohydrate-rich meal is consumed either 1 h before or after the exercise bout, probably due to a higher insulin concentration than found in the fasted state. In the postprandial exercise experiment (M→E), the glycerol and fatty acid releases increased about 150 min postexercise. The adrenaline concentration began to increase concomitantly, suggesting that it was the eliciting factor for the increased lipolysis. This is in accordance with what we have found previously in human subcutaneous adipose tissue about 4 h after an oral glucose intake during rest (Bülow et al. 1999). It can therefore be speculated that the delayed postexercise increase in the release rates of glycerol as well as fatty acids found postprandially is due to the hormonal counter regulation elicited by the meal and not to exercise per se.
In previous studies it has been demonstrated that there is a close correlation between the circulating fatty acid concentration and hepatic uptake of fatty acids (Havel et al. 1970; Ahlborg et al. 1974; Sidossis et al. 1999). In our previous study, during rest, we also found a tight co-ordination between adipose tissue and splanchnic lipid metabolism after glucose intake (Bülow et al. 1999). However, during exercise in the present experiments, it was not possible to demonstrate a positive correlation between the splanchnic fatty acid uptake and fatty acid delivery. One explanation of these findings is that the splanchnic uptake of fatty acids may be determined by factors other than the arterial blood concentration of fatty acids for the following reasons: the delivery of fatty acids during exercise in the postprandial exercise experiment (M→E) only decreased about 40% concomitant with a complete abolition of net splanchnic uptake of fatty acids; the net splanchnic uptake of fatty acids did not increase during exercise in the premeal exercise experiment (E→M) despite of a 25% increase in fatty acid delivery; and also postexercise, the net splanchnic uptake of fatty acids did not increase in consistency with the increased delivery in the postprandial exercise experiment (M→E). Another, and more likely, explanation is that an increased hepatic fatty acid uptake has been disguised by a concomitant increased release of fatty acids from the splanchnic adipose tissue depots (Van Hall et al. 2002; Jensen, 2003).
In our previous study during rest (Bülow et al. 1999), and in other studies (Havel et al. 1970; Lewis et al. 1995), it has been demonstrated that the splanchnic TAG output increases with an increased fatty acid uptake. However, we were not able to detect significant changes in the splanchnic TAG release in the present study. It has been well described that it may be difficult to detect changes in the splanchnic TAG net balance due to small venous-arterial differences approaching the detection limit of the TAG analysis (Jensen, 2003). Another possibility is that changes in the splanchnic release and uptake take place simultaneously and balance each other. An interesting finding in the present experiments is that exercise performed postprandially (M→E) led to a faster increase in the arterial total TAG concentration than was found in the preprandial exercise experiment (E→M). Different gastric emptying rates in the two experiments cannot explain this finding (Fig. 2). The faster increase is mostly due to an increase in the VLDL-TAG concentration as the chylomicron concentration increased equally fast in the two experiments (Table 2).
There is a large amount of evidence indicating that exercise performed ∼18 h prior to meal ingestion attenuates the postprandial lipaemia (Aldred et al. 1994; Zhang et al. 1998; Gill et al. 2001; Gill et al. 2003). Furthermore, studies in fasting subjects performed in our laboratory have shown that exercise per se leads to a reduction in the arterial TAG concentration immediately after exercise (Van Hall et al. 2002). In the present experiments it was not possible to demonstrate changes either in adipose tissue or in splanchnic TAG metabolism. Thus, a likely explanation for the more rapid increase in the TAG concentration is decreased clearance of TAG in the exercising skeletal muscles due to a higher availability of carbohydrates after food intake; however, this hypothesis should be tested in separate experiments. Generally, the present experiments show that moderate-intensity exercise performed shortly after a meal (M→E) leads to a less favourable metabolic state with respect to lipid combustion and circulating lipoprotein concentrations than exercise performed shortly before a meal (E→M).
In the postprandial exercise experiment (M→E), the carbohydrate-rich food intake led to an increase in the splanchnic glucose release during exercise, which was about 1 mmol min−1 higher than that found during exercise in the fasted state (E→M). Although it was not measured directly, this indicates that even when exercise is performed in the postprandial state with high glucose availability, an exercise-induced increase in splanchnic glucose production can be elicited.
The splanchnic oxygen consumption increased to the same extent postprandially in the experiments, but also with respect to oxygen consumption, there is an additive effect of food and exercise. Since the rate of oxidation of fatty acids to ketone bodies was very different in the two experimental series at comparable time points, it is unlikely that the fatty acid metabolism can explain the increase. However, the meal consisted of 20% protein, and absorption and metabolism of amino acids are major contributors to the increased postprandial splanchnic oxygen consumption (Brundin & Wahren, 1994).
In conclusion, while a carbohydrate-rich meal eaten 60 min before exercise of moderate intensity reduces whole-body lipid combustion rate to about 50% of the rate found during exercise in the fasted state, the anterior, abdominal, subcutaneous adipose tissue lipolytic rate during exercise is not influenced by previous food intake irrespective of different circulating insulin concentrations. However, the adipose tissue fatty acid release is reduced, and accordingly the intracellular adipose tissue fatty acid re-esterification is enhanced by the meal. Furthermore, food intake either 30 min after or 1 h before exercise prevents the postexercise increase in adipose tissue glycerol and fatty acid release, which takes place in fasting subjects, at least up to 2.5 h postprandially. At the whole-body level, moderate-intensity exercise performed 1 h after meal ingestion speeds up the increase of the postprandial arterial total TAG concentration. Thus, the present experiments indicate that exercise performed in the fasted state leads to a more favourable metabolic state with respect to lipid metabolism during exercise and during the postexercise recovery period than exercise performed shortly after a meal.
Acknowledgments
We thank Inge Rasmussen for excellent technical assistance. This study was supported by grants from the Novo Nordic Foundation, The John and Birthe Meyer Foundation, The Danish Medical Research Council (22-01-0235) and The Danish Heart Foundation (02-2-3-34-22016).
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