A single 1-h bout of evening exercise increases basal FFA flux without affecting VLDL-triglyceride and VLDL-apolipoprotein B-100 kinetics in untrained lean men

Our group (Magkos F, Wright DC, Patterson BW, Mohammed BS, Mittendorfer B, Am J Physiol Endocrinol Metab 290: E355-E362, 2006) has recently demonstrated that a single, prolonged bout of moderate-intensity cycling (2 h at 60% of peak oxygen consumption) in the evening increases basal whole-body free fatty acid (FFA) flux and fat oxidation, decreases hepatic VLDL-apolipoprotein B-100 (apoB-100) secretion, and enhances removal efficiency of VLDL-triglyceride (TG) from the circulation the following day in untrained, healthy, lean men. In the present study, we investigated the effect of a single, shorter-duration bout of the same exercise (1 h cycling at 60% of peak oxygen consumption) on basal FFA, VLDL-TG, and VLDL-apoB-100 kinetics in seven untrained, healthy, lean men by using stable isotope-labeled tracer techniques. Basal FFA rate of appearance in plasma and plasma FFA concentration were approximately 55% greater (P < 0.05) the morning after exercise than rest, whereas resting metabolic rate and whole-body substrate oxidation rates were not different after rest and exercise. Exercise had no effect on plasma VLDL-TG and VLDL-apoB-100 concentrations, hepatic VLDL-TG and VLDL-apoB-100 secretion rates, and VLDL-TG and VLDL-apoB-100 plasma clearance rates (all P > 0.05). We conclude that in untrained, healthy, lean men 1) the exercise-induced changes in basal whole-body fat oxidation, VLDL-TG, and VLDL-apoB-100 metabolism during the late phase of recovery from exercise are related to the duration of the exercise bout; 2) single sessions of typical recreational activities appear to have little effect on basal, fasting plasma TG homeostasis; and 3) there is a dissociation between systemic FFA availability and VLDL-TG and VLDL-apoB-100 secretion by the liver.     

Lipid metabolism response to a single, prolonged bout of endurance exercise in healthy young men

To discover the alterations in lipid metabolism linked to postexercise hypotriglyceridemia, we measured lipid kinetics, lipoprotein subclass distribution and lipid transfer enzymes in seven healthy, lean, young men the day after 2 h of cycling and rest. Compared with rest, exercise increased fatty acid rate of appearance and whole body fatty acid oxidation by approximately 65 and 40%, respectively (P < 0.05); exercise had no effect on VLDL-triglyceride (TG) secretion rate, increased VLDL-TG plasma clearance rate by 40 +/- 8%, and reduced VLDL-TG mean residence time by approximately 40 min and VLDL-apolipoprotein B-100 (apoB-100) secretion rate by 24 +/- 8% (all P < 0.05). Exercise also reduced the number of VLDL but almost doubled the number of IDL particles in plasma (P < 0.05). Muscle lipoprotein lipase content was not different after exercise and rest, but plasma lipoprotein lipase concentration increased by approximately 20% after exercise (P < 0.05). Plasma hepatic lipase and lecithin:cholesterol acyltransferase concentrations were not affected by exercise, whereas cholesterol ester transfer protein concentration was approximately 10% lower after exercise than after rest (P = 0.052). We conclude that 1) greater fatty acid availability after exercise does not stimulate VLDL-TG secretion, probably because of the increase in fatty acid oxidation and possibly also fatty acid use for restoration of tissue TG stores; 2) reduced secretion of VLDL-apoB-100 lowers plasma VLDL particle concentration; and 3) increased VLDL-TG plasma clearance maintains low plasma TG concentration but is not accompanied by similar increases in subsequent steps of the delipidation cascade. Acutely, therefore, the cardioprotective lowering of plasma TG and VLDL concentrations by exercise is counteracted by a proatherogenic increase in IDL concentration.     

Fatty acid reesterification but not oxidation is increased by oral contraceptive use in women.

We evaluated the hypothesis that fatty acid reesterification would be increased during rest and exercise in the midluteal menstrual cycle phase and during oral contraceptive use, when ovarian hormone concentrations are high, compared with the early follicular phase. Subjects were eight moderately active, weight-stable, eumenorrheic women (24.8 +/- 1.2 yr, peak oxygen consumption = 42.0 +/- 2.3 ml.kg(-1).min(-1)) who had not taken oral contraceptives for at least 6 mo. Plasma free fatty acid (FFA) kinetics were assessed in the 3-h postprandial state by continuous infusion of [1-(13)C]palmitate and [1,1,2,3,3-(2)H]glycerol during 90 min of rest and 60 min of exercise at 45% and 65% peak oxygen consumption in the early follicular and midluteal menstrual cycle phases and during the inactive- and high-dose phases following 4 mo of oral contraceptive use. Plasma FFA rates of appearance, disappearance, and oxidation increased significantly from rest to exercise with no differences noted between menstrual cycle or oral contraceptive phases or exercise intensities. Compared with either menstrual cycle phase, oral contraceptive use resulted in an increase in plasma-derived fatty acid reesterification and a decrease in the proportion of plasma FFA rate of disappearance that was oxidized at rest and during exercise. Endogenous and exogenous synthetic ovarian hormones do not exert a measurable influence on plasma FFA turnover or oxidation at rest or during moderate-intensity exercise in the 3-h postprandial state when carbohydrate use predominates. The increase in whole body lipolytic rate during exercise noted previously with oral contraceptive use is not matched by an increase in fatty acid oxidation and results in an increase in reesterification. Synthetic ovarian hormones contained in oral contraceptives increase lipolytic rate, but fatty acid oxidation during exercise is determined by exercise intensity and its metabolic and endocrine consequences.     

Acute exposure to GH during exercise stimulates the turnover of free fatty acids in GH-deficient men.

The secretion of growth hormone (GH) increases acutely during exercise, but whether this is associated with the concomitant alterations in substrate metabolism has not previously been studied. We examined the effects of acute GH administration on palmitate, glucose, and protein metabolism before, during, and after 45 min of moderate-intensity aerobic exercise in eight GH-deficient men (mean age = 40.8 +/- 2.9 yr) on two occasions, with (+GH; 0.4 IU GH) and without GH administered (-GH). A group of healthy controls (n = 8, mean age = 40.4 +/- 4.2 yr) were studied without GH. The GH replacement during exercise on the +GH study mimicked the endogenous GH profile seen in healthy controls. No significant difference in resting free fatty acid (FFA) flux was found between study days, but during exercise a greater FFA flux was found when GH was administered (211 +/- 26 vs. 168 +/- 28 micromol/min, P < 0.05) and remained elevated throughout recovery (P < 0.05). With GH administered, the exercise FFA flux was not significantly different from that observed in control subjects (188 +/- 14 micromol/min), but the recovery flux was greater on the +GH day than in the controls (169 +/- 17 vs. 119 +/- 11 micromol/min, respectively, P < 0.01). A significant time effect (P < 0.01) for glucose rate of appearance from rest to exercise and recovery occurred in the GH-deficient adults and the controls, whereas there were no differences in glucose rate of disappearance. No significant effect across time was found for protein muscle balance. In conclusion, 1) acute exposure to GH during exercise stimulates the FFA release and turnover in GH-deficient adults, 2) GH does not significantly impact glucose or protein metabolism during exercise, and 3) the exercise-induced secretion of GH plays a significant role in the regulation of fatty acid metabolism.     

High-intensity interval aerobic training reduces hepatic very low-density lipoprotein-triglyceride secretion rate in men

A single bout of strenuous endurance exercise reduces fasting plasma triglyceride (TG) concentrations the next day (12-24 h later) by augmenting the efficiency of very low-density lipoprotein (VLDL)-TG removal from the circulation. Although much of the hypotriglyceridemia associated with training is attributed to the last bout of exercise, the relevant changes in VLDL-TG metabolism have never been investigated. We therefore examined basal VLDL-TG kinetics in a group of sedentary young men (n=7) who underwent 2 mo of supervised high-intensity interval training (3 sessions/wk; running at 60 and 90% of peak oxygen consumption in 4-min intervals for a total of 32 min; gross energy expenditure: 446+/-29 kcal) and a nonexercising control group (n=8). Each subject completed two stable isotope-labeled tracer infusion studies in the postabsorptive state, once before and again after the intervention (approximately 48 h after the last exercise bout in the training group). Peak oxygen consumption increased by approximately 18% after training (P 0.7) in VLDL-TG plasma clearance rate and the mean residence time of VLDL-TG in the circulation. No significant changes in VLDL-TG concentration and kinetics were observed in the nonexercising control group (all P >or= 0.3). We conclude that a short period of high-intensity interval aerobic training lowers the rate of VLDL-TG secretion by the liver in previously sedentary men. This is different from the mechanism underlying the hypotriglyceridemia of acute exercise; however, it remains to be established whether our finding reflects an effect of the longer time lapse from the last exercise bout, an effect specific to the type of exercise performed, or an effect of aerobic training itself.     

Alterations in lipid kinetics in men with HIV-dyslipidemia

Hypertriglyceridemia is common in individuals with human immunodeficiency (HIV) infection, but the mechanisms responsible for increased plasma triglyceride (TG) concentrations are not clear. We evaluated fatty acid and VLDL-TG kinetics during basal conditions and during a glucose infusion that resulted in typical postprandial plasma glucose and insulin concentrations in six men with HIV-dyslipidemia [body mass index (BMI): 28 +/- 2 kg/m2] and six healthy men (BMI: 26 +/- 2 kg/m2). VLDL-TG secretion and palmitate rate of appearance (Ra) in plasma were measured by using stable-isotope-labeled tracer techniques. Basal palmitate Ra and VLDL-TG secretion rates were greater (P < 0.01 for both) in men with HIV-dyslipidemia (1.04 +/- 0.07 micromol palmitate x kg-1 x min-1 and 5.7 +/- 0.6 micromol VLDL-TG x l plasma-1 x min-1) than in healthy men (0.67 +/- 0.08 micromol palmitate. kg-1 x min-1 and 3.0 +/- 0.5 micromol VLDL-TG x l plasma-1 x min-1). Basal VLDL-TG plasma clearance was lower in men with HIV-dyslipidemia (13 +/- 1 ml/min) than in healthy men (19 +/- 2 ml/min; P < 0.05). Glucose infusion decreased palmitate Ra (by approximately 50%) and the VLDL-TG secretion rate (by approximately 30%) in both groups, but the VLDL-TG secretion rate remained higher (P < 0.05) in subjects with HIV-dyslipidemia. These findings demonstrate that increased secretion of VLDL-TG and decreased plasma VLDL-TG clearance, during both fasting and fed conditions, contribute to hypertriglyceridemia in men with HIV-dyslipidemia. Although it is likely that increased free fatty acid release from adipose tissue contributes to the increase in basal VLDL-TG concentration, other factors must be involved, because insulin-induced suppression of lipolysis and systemic fatty acid availability did not normalize the VLDL-TG secretion rate.     

No effect of menstrual cycle phase on basal very-low-density lipoprotein triglyceride and apolipoprotein B-100 kinetics

Dyslipidemia, manifested by increased plasma triglyceride (TG), increased total and LDL-cholesterol concentrations and decreased HDL-cholesterol concentration, is an important risk factor for cardiovascular disease. Premenopausal women have a less atherogenic plasma lipid profile and a lower risk of cardiovascular disease than men, but this female advantage disappears after menopause. This suggests that female sex steroids affect lipoprotein metabolism. The impact of variations in the availability of ovarian hormones during the menstrual cycle on lipoprotein metabolism is not known. We therefore investigated whether very-low-density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 (apoB-100) kinetics are different during the follicular (FP) and luteal phases (LP) of the menstrual cycle. We studied seven healthy, premenopausal women (age 27 +/- 2 yr, BMI 25 +/- 2 kg/m(2)) once during FP and once during LP. We measured VLDL-TG, VLDL-apoB-100, and plasma free fatty acid (FFA) kinetics by using stable isotope-labeled tracers, VLDL subclass profile by nuclear magnetic resonance spectroscopy, whole body fat oxidation by indirect calorimetry, and the plasma concentrations of lipoprotein lipase (LPL) and hepatic lipase (HL) by ELISA. VLDL-TG and VLDL-apoB-100 concentrations in plasma, VLDL-TG and VLDL-apoB-100 secretion rates and mean residence times, VLDL subclass distribution, FFA concentration and rate of appearance in plasma, whole body substrate oxidation, and LPL and HL concentrations in plasma were not different during the FP and the LP. We conclude that VLDL-TG and VLDL-apoB-100 metabolism is not affected by menstrual cycle phase.     

Effect of weight loss on VLDL-triglyceride and apoB-100 kinetics in women with abdominal obesity

The effects of obesity and weight loss on lipoprotein kinetics were evaluated in six lean women [body mass index (BMI): 21 +/- 1 kg/m(2)] and seven women with abdominal obesity (BMI: 36 +/- 1 kg/m(2)). Stable isotope tracer techniques, in conjunction with compartmental modeling, were used to determine VLDL-triglyceride (TG) and apolipoprotein B-100 (apoB-100) secretion rates in lean women and in obese women before and after 10% weight loss. VLDL-TG and VLDL-apoB-100 secretion rates were similar in lean and obese women. Weight loss decreased the rate of VLDL-TG secretion by approximately 40% (from 0.41 +/- 0.05 to 0.23 +/- 0.03 micromol x kg fat-free mass(-1) x min(-1); P < 0.05). The relative decline in VLDL-TG produced from nonsystemic fatty acids, derived from intraperitoneal and intrahepatic TG, was greater (61 +/- 7%) than the decline in VLDL-TG produced from systemic fatty acids, predominantly derived from subcutaneous TG (25 +/- 8%; P < 0.05). Weight loss did not affect VLDL-apoB-100 secretion rate. We conclude that weight loss decreases the rate of VLDL-TG secretion in women with abdominal obesity, primarily by decreasing the availability of nonsystemic fatty acids. There is a dissociation in the effect of weight loss on VLDL-TG and apoB-100 metabolic pathways that may affect VLDL particle size.     

Stimulatory effects of leptin and muscle contraction on fatty acid metabolism are not additive

Leptin has been shown to acutely stimulate fatty acid oxidation and triacylglycerol hydrolysis in skeletal muscle. These effects are similar to those induced by muscle contraction alone. Several studies have demonstrated that, during aerobic exercise, plasma leptin concentrations are well maintained; however, none has examined whether the stimulatory effects of leptin and contraction on muscle lipid metabolism are additive. This is the first study to examine the direct effect of leptin on lipid and carbohydrate (CHO) metabolism in isolated oxidative muscle over a range of contraction intensities. We examined the effect of leptin (10 microg/ml) on the synthesis and degradation of muscle lipid pools [phospholipid (PL), diacylglycerol (DG), triacylglycerol (TG)] and palmitate oxidation in isolated resting and contracting (2, 8, and 20 tetani/min) soleus muscles. At rest, leptin increased fatty acid oxidation (+ 40%, P < 0.05) and TG hydrolysis (+ 47%, P < 0.05), while blunting TG esterification (-20%, P < 0.05). Glucose oxidation was unaffected at rest in the presence of leptin. During tetanic contraction, fatty acid oxidation (+20-114%, P < 0.05) and TG esterification (+ 19-33%, P < 0.05) as well as net TG utilization (+ 23%, P < 0.05) were all significantly increased. However, leptin was without further effect on any of these parameters during contraction. Net utilization of intramuscular glycogen, as well as glucose oxidation, was unaffected during contraction by leptin. The findings of the present study indicate that leptin has an important influence on lipid metabolism in resting muscle, but not during contraction.     

Muscle malonyl-CoA decreases during exercise

Malonyl-CoA, the inhibitor of carnitine acyltransferase I, is an important regulator of fatty acid oxidation and ketogenesis in the liver. Muscle carnitine acyltransferase I has previously been reported to be more sensitive to malonyl-CoA inhibition than is liver carnitine acyltransferase I. Fluctuations in malonyl-CoA concentration may therefore be important in regulating the rate of fatty acid oxidation in muscle during exercise. Male rats were anesthetized (pentobarbital via venous catheters) at rest or after 30 min of treadmill exercise (21 m/min, 15% grade). The gastrocnemius/plantaris muscles were frozen at liquid N2 temperature. Muscle malonyl-CoA decreased from 1.66 +/- 0.17 to 0.60 +/- 0.05 nmol/g during the exercise. This change was accompanied by a 31% increase in cAMP in the muscle. The decline in malonyl-CoA occurred before muscle glycogen depletion and before onset of hypoglycemia. Plasma catecholamines, corticosterone, and free fatty acids were all significantly increased during the exercise. This exercise-induced decrease in malonyl-CoA may be important for allowing the increase in muscle fatty acid oxidation during exercise.     

Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster.

The hamster was developed as a model to study very low density lipoprotein (VLDL) metabolism, since, as is the case in humans, the hamster liver was found to synthesize apoB-100 and not apoB-48. The effect of inhibiting fatty acid synthesis on the hepatic secretion of VLDL triglyceride (TG) and apolipoprotein (apo) B-100 in this model was then investigated. In an in vivo study, hamsters were fed a chow diet containing 0.15% TOFA (5-tetradecyloxy-2-furancarboxylic acid), an inhibitor of acetyl-CoA carboxylase. After 6 days of treatment, plasma triglyceride and cholesterol levels were decreased by 30.2% and 11.6%, respectively. When the secretion of VLDL-TG by the liver was measured in vivo after injection of Triton WR 1339, TOFA treatment was found to decrease VLDL-TG secretion by 40%. In subsequent in vitro studies utilizing cultured primary hamster hepatocytes, incubation with 20 microM TOFA for 4 h resulted in 98% and 76% inhibition in fatty acid and triglyceride synthesis, respectively; VLDL-TG secretion was decreased by 90%. When hepatocytes were pulsed with [3H]leucine, incubation with TOFA resulted in a 50% decrease in the incorporation of radiolabel into secreted VLDL apoB-100. The results of this study indicate that inhibition of intracellular triglyceride synthesis decreases the secretion of VLDL-TG and apoB-100, and does not result in the secretion of a dense, triglyceride-depleted lipoprotein.     

Effect of gender on lipid kinetics during endurance exercise of moderate intensity in untrained subjects

We evaluated lipid metabolism during 90 min of moderate-intensity (50% VO(2) peak) cycle ergometer exercise in five men and five women who were matched on adiposity (24 +/- 2 and 25 +/- 1% body fat, respectively) and aerobic fitness (VO(2) peak: 49 +/- 2 and 47 +/- 1 ml x kg fat-free mass(-1) x min(-1), respectively). Substrate oxidation and lipid kinetics were measured by using indirect calorimetry and [(13)C]palmitate and [(2)H(5)]glycerol tracer infusion. The total increase in glycerol and free fatty acid (FFA) rate of appearance (R(a)) in plasma during exercise (area under the curve above baseline) was approximately 65% greater in women than in men (glycerol R(a): 317 +/- 40 and 195 +/- 33 micromol/kg, respectively; FFA R(a): 652 +/- 46 and 453 +/- 70 micromol/kg, respectively; both P < 0.05). Total fatty acid oxidation was similar in men and women, but the relative contribution of plasma FFA to total fatty acid oxidation was higher in women (76 +/- 5%) than in men (46 +/- 5%; P < 0.05). We conclude that lipolysis of adipose tissue triglycerides during moderate-intensity exercise is greater in women than in men, who are matched on adiposity and fitness. The increase in plasma fatty acid availability leads to a greater rate of plasma FFA tissue uptake and oxidation in women than in men. However, total fat oxidation is the same in both groups because of a reciprocal decrease in the oxidation rate of fatty acids derived from nonplasma sources, presumably intramuscular and possibly plasma triglycerides, in women.     

Acute changes in triacylglycerol lipase activity of human adipose tissue during exercise

Although physical exercise is known to increase adipose tissue lipolysis, its effect on the activity of triacylglycerol (TG) lipase, the enzyme regulating TG breakdown, is not known. The aim of the present study was to monitor the acute changes in TG lipase activity of adipose tissue induced during moderate exercise. For this purpose a new assay, sensitive to the phosphorylation state of the enzyme, was developed. Ten young sedentary men cycled for 30 min at a heart rate of 120-130 beats min(-1). Needle adipose tissue biopsy was performed from the buttock area at rest, at 5, 15, and 30 min of exercise, as well as at 15 min of passive recovery. Five other men served as controls by being biopsied as above without exercising. TG lipase activity was determined by measuring the decrease of endogenous TG concentration during incubation of the homogenized tissue. TG lipase activity increased 6.4-fold above baseline at 5 min of exercise (P < 0.001) and fell gradually afterwards, whereas it did not change significantly in the control group. In conclusion, our data show that TG lipase activity in human adipose tissue peaks early during exercise and subsequently decreases despite the maintenance of the physical stimulus.     

The role of transhepatic bile salt flux in the control of hepatic secretion of triacylglycerol-rich lipoproteins in vivo in rodents

Bile salts (BS) have been shown to suppress the secretion of very-low-density lipoprotein-triglyceride (VLDL-TG) in rat and human hepatocytes in vitro. In the present study, we investigated whether the transhepatic BS flux affects VLDL-TG concentration and hepatic VLDL-TG secretion in vivo. In rats, the transhepatic BS flux was quantitatively manipulated by 1-week chronic bile diversion (BD), followed by intraduodenal infusion with taurocholate (TC) or saline for 6 h. In mice, the transhepatic BS flux was manipulated by a 3-week dietary supplementation with TC (0.5 wt.%) or cholestyramine (2 wt.%). In rats, BD followed by saline or TC infusion did not affect plasma triacylglycerol (TG) concentration, hepatic TG production rate or VLDL lipid composition, compared to control rats. In mice supplemented for 3 weeks with TC or cholestyramine, the transhepatic BS flux was increased by 335% and decreased by 48%, respectively, compared to controls. Among the three experimental groups of mice, an inverse relationship between transhepatic BS flux and either plasma TG concentration (R(2)=0.89) or VLDL-TG production rate (R(2)=0.87) was observed, but differences were relatively small. Present data support the concept that BS can reduce VLDL-TG concentration and inhibit hepatic TG secretion in vivo; however, this occurs only at supraphysiological transhepatic BS fluxes in mice.     

Effects of moderate intensity treadmill exercise on triglyceride production in the laying fowl

1. Sustained aerobic exercise in domestic fowl has previously been shown to enhance lipid utilization by the skeletal muscles. The present study examined the possibility that such increased lipid oxidation in the laying female might lower the production of plasma triglycerides destined for transfer to the developing oocytes. 2. Following an intravenous injection of 25 muCi of 14C-labelled glycerol trioleate, the experimental birds performed 90 min of treadmill exercise at a work intensity approximately equivalent to 2.5 times the resting metabolic rate. 3. There was no evidence of either glycogen or triglyceride depletion in either the leg muscles or the viscera of the exercised birds. The specific activity of triglyceride TG-SRA found in the tissues was also the same in control and experimental birds. The time-course of the changes in plasma TG-SRA throughout the experimental period gave no indication that TG production had been affected by exercise. 4. It is concluded that the increased energy substrate demand arising from moderate-intensity, aerobic exercise is almost fully met by the liberation of fatty acids from adipose tissue TG stores, and has minimal impact on the hepatic manufacture of egg lipids.     

Endurance training has little effect on active muscle free fatty acid, lipoprotein cholesterol, or triglyceride net balances

We evaluated the hypothesis that net leg total FFA, LDL-C, and TG uptake and HDL-C release during moderate-intensity cycling exercise would be increased following endurance training. Eight sedentary men (26 +/- 1 yr, 77.4 +/- 3.7 kg) were studied in the postprandial state during 90 min of rest and 60 min of exercise twice before (45% and 65% V(O2 peak)) and twice after 9 wk of endurance training (55% and 65% posttraining V(O2 peak)). Measurements across an exercising leg were taken to be a surrogate for active skeletal muscle. To determine limb lipid exchange, femoral arterial and venous blood samples drawn simultaneously at rest and during exercise were analyzed for total and individual FFA (e.g., palmitate, oleate), LDL-C, HDL-C, and TG concentrations, and limb blood flow was determined by thermodilution. The transition from rest to exercise resulted in a shift from net leg total FFA release (-44 +/- 16 micromol/min) to uptake (193 +/- 49 micromol/min) that was unaffected by either exercise intensity or endurance training. The relative net leg release and uptake of individual FFA closely resembled their relative abundances in the plasma with approximately 21 and 41% of net leg total FFA uptake during exercise accounted for by palmitate and oleate, respectively. Endurance training resulted in significant changes in arterial concentrations of HDL-C (49 +/- 5 vs. 52 +/- 5 mg/dl, pre vs. post) and LDL-C (82 +/- 9 vs. 76 +/- 9 mg/dl, pre vs. post), but there was no net TG or LDL-C uptake or HDL-C release across the resting or active leg before or after endurance training. In conclusion, endurance training favorably affects blood lipoprotein profiles, even in young, healthy normolipidemic men, but muscle contractions per se have little effect on net leg LDL-C, or TG uptake or HDL-C release during moderate-intensity cycling exercise. Therefore, the favorable effects of physical activity on the lipid profiles of young, healthy normolipidemic men in the postprandial state are not attributable to changes in HDL-C or LDL-C exchange across active skeletal muscle.     

The acute effects of differential dietary fatty acids on human skeletal muscle pyruvate dehydrogenase activity.

Pyruvate dehydrogenase (PDH) is an important regulator of carbohydrate oxidation during exercise, and its activity can be downregulated by an increase in dietary fat. The purpose of this study was to determine the acute metabolic effects of differential dietary fatty acids on the activation of the PDH complex (PDHa activity) at rest and at the onset of moderate-intensity exercise. University-aged male subjects (n = 7) underwent two fat-loading trials spaced at least 2 wk apart. Subjects consumed approximately 300 g saturated (SFA) or n-6 polyunsaturated fatty acid (PUFA) fat over the course of 5 h. Following this, participants cycled at 65% of their maximum oxygen uptake for 15 min. Muscle biopsies were taken before and following fat loading and at 1 min exercise. Plasma free fatty acids increased from 0.15 +/- 0.07 to 0.54 +/- 0.19 mM over 5 h with SFA and from 0.11 +/- 0.04 to 0.35 +/- 0.13 mM with n-6 PUFA and were significantly lower throughout the n-6 PUFA trial. PDHa activity was unchanged following fat loading but increased at the onset of exercise in the SFA trial, from 1.18 +/- 0.27 to 2.16 +/- 0.37 mmol x min(-1) x kg wet wt(-1). This effect was negated in the n-6 PUFA trial (1.04 +/- 0.20 to 1.28 +/- 0.36 mmol x min(-1) x kg wet wt(-1)). PDH kinase was unchanged in both trials, suggesting that the attenuation of PDHa activity with n-6 PUFA was a result of changes in the concentrations of intramitochondrial effectors, potentially intramitochondrial NADH or Ca(2+). Our findings suggest that attenuated PDHa activity contributes to the preferential oxidation of n-6 PUFA during moderate-intensity exercise.     

Energy substrate partitioning and efficiency in individuals with atherogenic lipoprotein phenotype

Individuals with an atherogenic lipoprotein phenotype (ALP) characterized by increased levels of small dense low-density lipoprotein (LDL) particles tend to have greater adiposity compared to unaffected subjects. We sought to determine whether this may be related to alterations in energy substrate partitioning or efficiency. These were assessed by indirect calorimetry in men with ALP (ALP(+), n = 7) and unaffected controls (ALP(-), n = 8) during rest (30 min) and exercise (10 min). Gross, net and delta efficiencies were calculated during graded leg-cycle ergometry at workloads of 10 and 50 W. Respiratory exchange ratios (RER) were significantly (P < 0.05) higher in ALP(+) vs. ALP(-) during rest (0.86 ± 0.01 vs. 0.83 ± 0.02) and exercise at 10 W (0.88 ± 0.02 vs. 0.84 ± 0.02) and 50 W (0.92 ± 0.01 vs. 0.87 ± 0.01, respectively) (P < 0.05). Lipid oxidation (kcal/min) was lower in ALP(+) vs. ALP(-) during rest (0.56 ± 0.02 vs. 0.71 ± 0.07) and exercise at 10 W (1.52 ± 0.25 vs. 2.00 ± 0.20) and 50 W (1.28 ± 0.10 vs. 2.32 ± 0.22, respectively) (P < 0.05). Gross and net efficiencies were significantly increased (P = 0.005) in ALP(+) vs. ALP(-) at 10 W. RER was correlated positively with plasma triglyceride during exercise and inversely with high-density lipoprotein (HDL) cholesterol and LDL peak particle diameter during rest and exercise (P < 0.05). These findings suggest that increased muscular efficiency at low exercise intensity and reduced lipid oxidation during rest and exercise may contribute to both dyslipidemia and increased adiposity in individuals with ALP.     

Lactate production under fully aerobic conditions: the lactate shuttle during rest and exercise

O2 insufficiency and other factors increase the rate of lactate production. Significant quantities of lactate are produced under postabsorptive as well as postprandial conditions in resting individuals. In humans during postabsorptive rest, 25-50% of the total carbohydrate combusted appears to pass through the lactate pool. During sustained submaximal (in terms of VO2max) exercise, the rates of lactate production (Ri) and oxidation (Rox) are greatly elevated as compared to rest. However, lactate production and oxidation increase relatively less than O2 consumption during moderate-intensity exercise. Because the lactate production index (RiI = Ri/VO2) decreases during submaximal, moderate-intensity exercise compared to rest, it is concluded that skeletal muscle and other sites of lactate production are effectively oxygenated. Alterations in the levels of circulating catecholamines can affect levels and turnover rates of glucose and lactate. In pure red dog gracilis muscle in situ and in the healthy and myocardium in vivo, contraction results in glycolysis and lactate production. This production of lactate occurs despite an apparent abundance of O2. Similarly, glucose catabolism in the human brain results in lactate production. The formation of lactate under fully aerobic conditions of rest and exercise represents an important mechanism by which different tissues share a carbon source (lactate) for oxidation and other processes such as gluconeogenesis. This mechanism has been termed the lactate shuttle.     

Effects of adenosine, exercise, and moderate acute hypoxia on energy substrate utilization of human skeletal muscle

Glucose metabolism increases in hypoxia and can be influenced by endogenous adenosine, but the role of adenosine for regulating glucose metabolism at rest or during exercise in hypoxia has not been elucidated in humans. We studied the effects of exogenous adenosine on human skeletal muscle glucose uptake and other blood energy substrates [free fatty acid (FFA) and lactate] by infusing adenosine into the femoral artery in nine healthy young men. The role of endogenous adenosine was studied by intra-arterial adenosine receptor inhibition (aminophylline) during dynamic one-leg knee extension exercise in normoxia and acute hypoxia corresponding to ～3,400 m of altitude. Extraction and release of energy substrates were studied by arterial-to-venous (A-V) blood samples, and total uptake or release was determined by the product of A-V differences and muscle nutritive perfusion measured by positron emission tomography. The results showed that glucose uptake increased from a baseline value of 0.2 ± 0.2 to 2.0 ± 2.2 μmol·100 g(-1)·min(-1) during adenosine infusion (P < 0.05) at rest. Although acute hypoxia enhanced arterial FFA levels, it did not affect muscle substrate utilization at rest. During exercise, glucose uptake was higher (195%) during acute hypoxia compared with normoxia (P = 0.058), and aminophylline had no effect on energy substrate utilization during exercise, despite that arterial FFA levels were increased. In conclusion, exogenous adenosine at rest and acute moderate hypoxia during low-intensity knee-extension exercise increases skeletal muscle glucose uptake, but the increase in hypoxia appears not to be mediated by adenosine.