Lipoproteins are small triglyceride (TG), cholesterol and phospholipids containing particles. There are five lipoproteins. Lipoproteins are classified by their densities. Chylomicrons (0.95 g-1 • cm-3) are briefly postprandial present in the bloodplasma and synthesized by the mucosacells of the small intestines. Chylomicrons are the biggest lipoproteins and contain predominantly TG. VLDL (0.95-1.006 g-1 • cm-3) are being synthesized in the liver and contains de novo synthesized TG and cholesterol. VLDL (and chylomicrons) are being hydrolyzed by lipoprotein lipase (LPL). Intermediate Density Lipoprotein (IDL) (1.006-1.019 g-1 • cm-3) is a catabolic product of VLDL and is for 50% absorbed by the liver and for 50% transformed in Low Density Lipoprotein (LDL). LDL (1.019-1.063 g-1 • cm-3) is being synthesized by the liver and contains a mass of cholesterolesters. Around the core of cholesterolesters LDL contains a coat of phospholipids and only one copy of Apoprotein B100. LDL is being used by peripheral cells that extract cholesterol from the LDL-particle. High Density Lipoproteins (HDL) (1.063-1.21 g-1 • cm-3) are synthesized by the liver and contain large amounts of Apoprotein A1 and A2. HDL extracts cholesterol out of peripheral cells and transports it to the liver.
After an overnight fast roughly 50% of plasma TG are found in VLDL. VLDL is the main carrier of TG in fasting plasma and is strongly dependent on the delivery of FFA, the main substrate for VLDL-TG synthesis.
The muscle, heart and adipose tissue contain LPL at the endothelial site of the capillaries where it hydrolyzes TG carried by plasma TG, yielding fatty acids for localized uptake by these tissues.
Plasma TG could represent a potentially rich source of fatty acids for the exercising muscle. There is conflicting evidence, however, concerning the role of plasma TG in moderate intensity exercise.
Some researchers found no statistical significant decrease of arterial-venous (a-v) difference of plasma TG in exercising dogs or humans. This indicates that no plasma TG are taken up and oxidized by the exercising muscle. However, one study, where the VLDL-TG oxidation contributed less than 5% to total fat oxidation the catherization places were not mentioned so the site of metabolism was not clear. In one study the jugular vein and carotid artery were catherized, at these places the metabolism is different from the metabolism of the exercising muscle. In two studies the femoral vein was catherized.
It is known that results obtained from a-v difference from the femoral vein should be carefully interpreted.
There appears to be systematic difference in the concentrations of FFA and glycerol when measured distally or proximally in the femoral vein. This difference can be a major problem. In the distal direction glycerol and FFA levels are lower than those in the slightly more proximal position. The femoral vein blood sample will not only represent blood from the active skeletal muscle but also from fat deposits outside the active skeletal muscle. A-v differences could also be undetected, but physiologic important. In contrast to the above mentioned researchers and keeping the methodological considerations of Van Hall et al. in mind, Wolfe et al. observed that VLDL-TG oxidation contributed 15% of total energy metabolism during rest. Wolfe et al. studied the role of VLDL-TG in energy metabolism of conscious, 24-hr fasted rats. Labelled [2-2H]-glycerol and [1-14H]-palmitate were infused into the rats, along with [1-13H]-palmitate bound to albumin and d-8-glycerol. Also a-v differences of VLDL-TG and plasma FFA were measured. The oxidation of plasma glucose accounted for 7% of total energy expenditure (EE). Muscle glycogen oxidation was thought to be minimal. The oxidation of VLDL-TG derived fatty acids accounted for approximately 15% of total energy expenditure, which was roughly the same as the percentage EE arising from plasma FFA oxidation. Therefore, IMTG oxidation accounted for more than 50% of total EE.
Helge et al. also using the a-v difference technique, found that VLDL-TG accounts for the increased fat oxidation observed during exercise after fat adaptation . Helge et al. studied 13 male untrained subjects, of which seven consumed a fat-rich diet and six consumed a carbohydrate-rich diet. After seven weeks of training and diet, moderate intensity exercise was performed. During exercise [1-13C]-palmitate was infused, arterial and venous blood samples were collected. VLDL-TG appeared to be an important substrate source during moderate intensity exercise, and in combination with the higher plasma FFA uptake it accounts for the 11% increased fat oxidation during exercise after fat diet adaptation.
As earlier mentioned LPL hydrolyzes plasma TG. Attention has focused on muscle LPL activity. LPL is found in many tissues including skeletal muscle, adipose tissue and cardiac muscle. LPL hydrolyzes TG carried by lipoproteins, yielding fatty acids for localized uptake by tissues. Heterozygos LPL knockout mice have 50% of normal LPL enzyme activity, but are hyper triglyceridemic. This suggests that LPL could be rate-limiting for the transport of fatty acids derived from plasma TG into skeletal muscle. Given its large mass, dense capillaries and relatively high resting blood flow relative to fat, skeletal muscle is probably the dominant source of LPL. The LPL activity of muscles (mLPL) seems to be related to the oxidative capacity of these muscles. mLPL activity in slow-twitch red fibres is approximately 14- to 20 fold higher than that in fast twitch white and approximately 2-fold higher than in fast red fibres of untrained rats and mLPL expression is several times greater in a red (soleus) than in a white muscle of the rat. This indicates that type 1 muscle fibres are more capable for plasma TG clearance and oxidation. Although mLPL activity seems to be related to muscle oxidative capacity high plasma FFA levels inhibit mLPL activity and would inhibit plasma TG-hydrolysis. Plasma FFA concentration are high during moderate intensity exercise. High plasma FFA concentration would inhibit the clearance of plasma TG. However, it is also clear that high FFA oxidation rates facilitates mLPL activity, and TG-hydrolysis would be stimulated. FFA oxidation rates are very high during moderate intensity exercise (40-65%VO2max). This would stimulate plasma TG clearance. Also whole fat oxidation is positively related to mLPL-activity. As exercise intensity is increased up to 65%VO2max the absolute contribution of fat oxidation to total EE reaches maximum rates. The high contribution of fat oxidation to total energy expenditure would also stimulate plasma TG clearance. However, it is not clear which effect plasma FFA concentration and total fat oxidation have on plasma TG clearance.
Long term regular exercise has considerable potential to enhance muscle TG uptake via 1) increases in muscle mass and 2) structural changes in its microcirculation. Endurance trained individuals have more capillaries per unit cross-sectional area of muscle. Also in men who trained one leg but not the other at 65%VO2max for 8 weeks, capillarisation was 20% greater in muscle from the trained leg than from the untrained contralateral leg, with 35-46% higher mLPL-activity. Moreover, mLPL-activity was related to capillary density. The acquisition of fatty acids is thus facilitated in trained muscle. Also training male rats on a treadmill for 6 or 12 weeks leads to an increase in mLPL-activity, and detraining healthy athletes for a period of 2 weeks resulted in a decrease in mLPL-activity. Long term endurance training increases mLPL-activity (and VLDL-TG clearance). However, acute aerobic exercise also has a facilitating effect on mLPL-activity which may also be further enhanced in trained individuals who perform acute endurance exercise. Male runners participating in a marathon had reductions in their serum TG levels 18, 42 and 66 hours after the race. However, following acute 1 hour one-leg knee-extension exercise no change in mLPL-activity was found immediately after exercise. One explanation for these apparently conflicting findings is that to stimulate mLPL-activity, muscle-contractions and adequate amounts of plasma catecholamines (knee extension exercise evokes little catecholamine) are needed.
Attention has also focused on HDL-cholesterol in relation to mLPL-activity and the plasma TG clearance capacity by the muscle. The reason for this is that high concentrations of TG-rich lipoproteins provide increased opportunity for exchange with cholesterylesters from HDL, and as a consequence the cholesterol measured in HDL decreases. However, when plasma TG-rich lipoproteins concentration decreases (maybe by enhanced muscle uptake and oxidation) HDL increases. It is proven that exercise can increase HDL-cholesterol after exercise and could enhance the clearance-rate of plasma TG.
The contribution of plasma TG to the energy requirement of skeletal muscles may be more significant during prolonged exercise. This is suggested by the fall in plasma TG levels and the increased levels of mLPL-activity after an 85-km ski race and after cross-country marching for several hours. The lowering of plasma TG is seen immediately after work if the exercise is vigorous over an extended period of time. Even though plasma TG stores are lowered immediately after exercise, the actual energy contribution to the work performed appears to be relatively small. Plasma TG should only provide 4% of the energy required during moderate intensity exercise (40-65%VO2max). However, it should be pointed out that plasma FFA levels are high during moderate intensity exercise (40-65%VO2max). Therefore, TG synthesis can take place in the liver during moderate intensity exercise. Hepatic TG synthesis would serve to underestimate the contribution of plasma TG to the total amount of energy expended during moderate intensity exercise (40-65%VO2max).
The lowering of plasma TG could be attributable to a specific effect of exercise on lipid metabolism or to a decreased availability of substrate for plasma TG synthesis secondary to the increased energy expenditure. However, plasma TG are reduced despite an increased food intake, indicating that the plasma TG-lowering effect of exercise is not mediated by a negative caloric intake.
LPL appears to have an important role in providing fatty acids for intracellular TG in muscle. It is known that the uptake of plasma TG is highly related to mLPL-activity. In this context mLPL–activity is markedly increased with exercise training. Also, LPL-deficient mice develop severe hyperchylomicronemia because of an inability to clear plasma TG. These affected mice have no intracellular lipid droplets in the heart and diaphragm, whereas unaffected mice have numerous lipid droplets in these muscle cells. The finding that exercise increases the capacity to clear plasma TG provides suggestive evidence that LPL could also be major regulating factor in the restoration of muscle TG stores.
Though more research is warranted, the available literature suggests that plasma TG play a major role in fat metabolism during and after moderate intensity exercise. The regulation of LPL activity in skeletal muscle has important implications for the disposal of lipoprotein derived triglyceride. In skeletal muscle LPL activity depends on the fibre type, being highest in red muscles, and the lowest in white muscle. These differences are due to differences in the contractile muscle activity and preferences for lipid substrate as the energy source in red fibres. Enhanced physical activity increases mLPL activity. This suggests that mLPL plays a major role during and after exercise in providing the muscle with fatty acids for oxidation and/or restoration of muscle TG stores.
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