Plasma Fatty Acid Availability Research Articles

The Importance of Fatty Acids as Nutrients during Post-Exercise Recovery.

It is well recognized that whole-body fatty acid (FA) oxidation remains increased for several hours following aerobic endurance exercise, even despite carbohydrate intake. However, the mechanisms involved herein have hitherto not been subject to a thorough evaluation. In immediate and early recovery (0–4 h), plasma FA availability is high, which seems mainly to be a result of hormonal factors and increased adipose tissue blood flow. The increased circulating availability of adipose-derived FA, coupled with FA from lipoprotein lipase (LPL)-derived very-low density lipoprotein (VLDL)-triacylglycerol (TG) hydrolysis in skeletal muscle capillaries and hydrolysis of TG within the muscle together act as substrates for the increased mitochondrial FA oxidation post-exercise. Within the skeletal muscle cells, increased reliance on FA oxidation likely results from enhanced FA uptake into the mitochondria through the carnitine palmitoyltransferase (CPT) 1 reaction, and concomitant AMP-activated protein kinase (AMPK)-mediated pyruvate dehydrogenase (PDH) inhibition of glucose oxidation. Together this allows glucose taken up by the skeletal muscles to be directed towards the resynthesis of glycogen. Besides being oxidized, FAs also seem to be crucial signaling molecules for peroxisome proliferator-activated receptor (PPAR) signaling post-exercise, and thus for induction of the exercise-induced FA oxidative gene adaptation program in skeletal muscle following exercise. Collectively, a high FA turnover in recovery seems essential to regain whole-body substrate homeostasis.

Repeated Prolonged Exercise Decreases Maximal Fat Oxidation in Older Men.

Fat metabolism and muscle adaptation was investigated in six older trained men (age, 61 ± 4 yr; V˙O2max, 48 ± 2 mL·kg·min) after repeated prolonged exercise). A distance of 2706 km (1681 miles) cycling was performed over 14 d, and a blood sample and a muscle biopsy were obtained at rest after an overnight fast before and 30 h after the completion of the cycling. V˙O2max and maximal fat oxidation were measured using incremental exercise tests. HR was continuously sampled during cycling to estimate exercise intensity. The daily duration of exercise was 10 h and 31 ± 37 min, and the mean intensity was 53% ± 1% of V˙O2max. Body weight remained unchanged. V˙O2max and maximal fat oxidation rate decreased by 6% ± 2% (P = 0.04) and 32% ± 8% (P < 0.01), respectively. The exercise intensity that elicits maximal fat oxidation was not significantly decreased. Plasma free fatty acid (FA) concentration decreased (P < 0.002) from 500 ± 77 μmol·L to 160 ± 38 μmol·L. Plasma glucose concentration as well as muscle glycogen, myoglobin, and triacylglycerol content remained unchanged. Muscle citrate synthase and ß-hydroxy-acyl-CoA-dehydrogenase activities were unchanged, but the protein expression of HKII, GLUT4, and adipose triacylglycerol lipase were significantly increased. Overall, the decreased maximal fat oxidation was probably due to lower exogenous plasma fatty acid availability and the muscle adaptation pattern indicates an increased glucose transport capacity and an increased muscle lipolysis capacity supporting an increased contribution of exogenous glucose and endogenous fat during exercise.

Effect of DHA on plasma fatty acid availability and oxidative stress during training season and football exercise.

The aim was to determine the effects of a diet supplemented with 1.14 g per day of docosahexaenoic acid (DHA) for eight weeks on the plasma oxidative balance and anti-inflammatory markers after training and acute exercise. Fifteen volunteer male football players were randomly assigned to placebo or experimental and supplemented groups. Blood samples were taken under resting conditions at the beginning and after eight weeks of training under resting and post-exercise conditions. The experimental beverage increased the plasma DHA availability in non-esterified fatty acids (NEFAs) and triglyceride fatty acids (TGFAs) and increased the polyunsaturated fatty acid (PUFA) fraction of NEFAs but had no effects on the biomarkers for oxidative balance in plasma. During training, plasma protein markers of oxidative damage, the haemolysis degree and the antioxidant enzyme activities increased, but did not affect lipid oxidative damage. Training season and DHA influenced the circulating levels of prostaglandin E2 (PGE2). Acute exercise did not alter the basal levels of plasma markers for oxidative and nitrosative damage of proteins and lipids, and the antioxidant enzyme activities, although DHA-diet supplementation significantly increased the PGE2 in plasma after acute exercise. In conclusion, the training season and acute exercise, but not the DHA diet supplementation, altered the pattern of plasma oxidative damage, as the antioxidant system proved sufficient to prevent the oxidative damage induced by the acute exercise in well-trained footballers. The DHA-diet supplementation increased the prostaglandin PGE2 plasma evidencing anti-inflammatory effects of DHA to control inflammation after acute exercise.

Increased fat oxidation and regulation of metabolic genes with ultraendurance exercise

Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes. Data were obtained from 11 competitors of a 4- to 5-day, almost continuous ultraendurance race (seven males, four females; age: 36 +/- 11 years; cycling Vo(2peak): males 57.4 +/- 5.9, females 48.1 +/- 4.0 mL kg(-1) min(-1)). Before and after the race muscle biopsies were obtained from vastus lateralis, respiratory gases were sampled during cycling at 25 and 50% peak aerobic power output, venous samples were obtained, and fat mass was estimated by bioimpedance under standardized conditions. After the race fat mass was decreased by 1.6 +/- 0.4 kg (11%; P < 0.01). Respiratory exchange ratio at the 25 and 50% workloads decreased (P < 0.01) from 0.83 +/- 0.06 and 0.93 +/- 0.03 before, to 0.71 +/- 0.01 and 0.85 +/- 0.02, respectively, after the race. Plasma fatty acids were 3.5 times higher (from 298 +/- 74 to 1407 +/- 118 micromol L(-1); P < 0.01). Muscle glycogen content fell 50% (from 554 +/- 28 to 270 +/- 25 nmol kg(-1) d.w.; n = 7, P < 0.01), whereas the decline in muscle triacylglycerol (from 32 +/- 5 to 22 +/- 3 mmol kg(-1) d.w.; P = 0.14) was not statistically significant. After the race, muscle mRNA content of lipoprotein lipase and glycogen synthase increased (P < 0.05) 3.9- and 1.7-fold, respectively, while forkhead homolog in rhabdomyosarcoma, pyruvate dehydrogenase kinase 4 and vascular endothelial growth factor mRNA tended (P < 0.10) to be higher, whereas muscle peroxisome proliferator-activated receptor gamma co-activator-1beta mRNA tended to be lower (P = 0.06). Very prolonged exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes.

Reduced plasma free fatty acid availability during exercise: effect on gene expression

Endurance exercise transiently increases the mRNA of key regulatory proteins involved in skeletal muscle metabolism. During prolonged exercise and subsequent recovery, circulating plasma fatty acid (FA) concentrations are elevated. The present study therefore aimed to determine the sensitivity of key metabolic genes to FA exposure, assessed in vitro using L6 myocytes and secondly, to measure the expression of these same set of genes in vivo, following a single exercise bout when the post-exercise rise in plasma FA is abolished by acipimox. Initial studies using L6 myotubes demonstrated dose responsive sensitivity for both PDK4 and PGC-1alpha mRNA to acute FA exposure in vitro. Nine active males performed two trials consisting of 2 h exercise, followed by 2 h of recovery. In one trial, plasma FA availability was reduced by the administration of acipimox (LFA), a pharmacological inhibitor of adipose tissue lipolysis, and in the second trial a placebo was provided (CON). During the exercise bout and during recovery, the rise in plasma FA and glycerol was abolished by acipimox treatment. Following exercise the mRNA abundance of PDK4 and PGC-1alpha were elevated and unaffected by either acipimox or placebo. Further analysis of skeletal muscle gene expression demonstrated that the CPT I gene was suppressed in both trials, whilst UCP-3 gene was only modestly regulated by exercise alone. Acipimox ingestion did not alter the response for both CPT I and UCP-3. Thus, this study demonstrates that the normal increase in circulating concentrations of FA during the later stages of exercise and subsequent recovery is not required to induce skeletal muscle mRNA expression of several proteins involved in regulating substrate metabolism.

Postexercise insulin sensitivity is not impaired after an overnight lipid infusion

High plasma fatty acid availability and a positive energy balance in sedentary individuals reduce insulin sensitivity. This study's purpose was to determine whether high plasma fatty acid availability and systemic caloric excess after exercise also impair insulin sensitivity. On two separate occasions, seven nonobese women performed 90 min of exercise at approximately 65% peak oxygen uptake. In one trial, a lipid + heparin emulsion (Lipid) was infused overnight to increase plasma fatty acid availability. In the other trial, saline was infused as control. The next morning, a muscle biopsy was taken to measure muscle glycogen and intramuscular triglyceride (IMTG) concentrations. Three hours after the overnight infusion was stopped, insulin sensitivity was assessed with an intravenous glucose tolerance test, using minimal model analysis (Si). During the overnight infusions, plasma fatty acid concentration was approximately fourfold higher [means (SD): 0.84 (0.36) vs. 0.22 (0.09) mmol/l; P = 0.003], and the next morning IMTG concentration was approximately 30% greater [49.2 (6.6) vs. 38.3 (7.7) mmol/kg dry wt; P = 0.036] in Lipid compared with saline. However, muscle glycogen concentration was not different between trials (P = 0.82). Lipid caused a 24-h surplus of approximately 1100 kcal above energy balance (P = 0.00001), whereas energy balance was maintained in saline. Despite these differences in fatty acid and energy availability, Si the morning after exercise was not different between trials (P = 0.72). Thus insulin sensitivity the morning after a single exercise session was not reduced despite overnight exposure to a fourfold increase in plasma fatty acid concentration, elevated IMTG concentration, and systemic delivery of approximately 1,100-kcal excess.

Post-exercise Insulin Sensitivity is Not Impaired After an Overnight Lipid Infusion

2266 An increase in plasma fatty acid availability reduces insulin sensitivity. It is unclear, however, if this inhibitory effect persists after plasma FA concentrations return to basal levels. PURPOSE: To determine whether overnight exposure to elevated plasma fatty acid concentrations after exercise alters insulin sensitivity the next morning. METHODS: Four healthy women exercised for 90 min at ∼65% VO2peak on two separate occasions. On one occasion a 20% lipid emulsion with heparin was infused (LIPID; 0.11 g fat/kg/h) from 1500h on the day of exercise until 0700h the next morning. On the other occasion, saline was infused as a control (SALINE). On both occasions subjects ingested the same meals after exercise (82% carbohydrate, 7% fat, 11% protein; 2661 ± 189 kcal/day), which was designed to maintain energy balance. Hourly blood samples were taken overnight for measurement of plasma fatty acid concentrations. At 0900h, 2 h after stopping the overnight infusion, a blood sample was obtained to measure plasma fatty acid, glucose and insulin concentrations, followed immediately by an intravenous glucose tolerance test to assess insulin sensitivity (Si and AIRG) using minimal model analysis. Indirect calorimetry was used to estimate resting and exercise energy expenditure. RESULTS: Total 24 h energy expenditure was not different in SALINE and LIPID (2424 ± 57 vs. 2309 ± 93 kcals). The lipid infusion, however, increased systemic caloric availability by 1417 ± 231 kcal and the average overnight plasma fatty acid concentration was 4-fold higher during LIPID than SALINE (0.87 ± 0.08 vs. 0.22 ± 0.03 mM, p<0.05). Two h after stopping the overnight infusions, plasma fatty acid concentrations returned to basal levels and were similar in SALINE and LIPID (0.49 ± 0.17 vs. 0.30 ± 0.17 mM), as were the plasma glucose (4.7 ± 0.1 vs. 4.9 ± 0.4 mM) and insulin concentrations (9.9 ± 2.3 vs. 12.5 ± 3.2 μU/mL). Insulin sensitivity (Si: 7.3 ± 1.9 vs. 7.8 ± 2.3 [×10-4 min−1/(μU/mL)] and the insulin response to glucose (AIRG: 602.7 ± 260.2 vs. 661.0 ± 296.8 μU/mL×10min) were also not different. CONCLUSIONS: Insulin sensitivity the morning after a single exercise session was not reduced after overnight exposure to a 4-fold increase in plasma fatty acid concentration and the delivery of ∼1400 excess calories. Funding sources: NIH – NIDDK #5P60DK-20572 and NIH #M01-RR00042

Effect of sex and obesity on basal VLDL-triacylglycerol kinetics

Plasma fatty acid availability is a major regulator of VLDL-triacylglycerol production. Basal whole-body lipolysis is higher in women than in men and is higher in persons with abdominal obesity than in lean individuals. Our goal was to determine whether sex and abdominal obesity affect VLDL-triacylglycerol kinetics. We hypothesized that basal VLDL-triacylglycerol production would be greater in women than in men and greater in obese than in lean subjects. VLDL-triacylglycerol kinetics were measured in 20 lean (10 men, 10 women; body mass index, in kg/m(2): 23 +/- 1) and 20 abdominally obese (10 men, 10 women; body mass index: 35 +/- 1) subjects by using a bolus injection of [(2)H(5)]glycerol and compartmental modeling analysis. The rate of VLDL-triacylglycerol secretion was greater in the lean women than in the lean men (5.1 +/- 0.7 and 2.6 +/- 0.3 micro mol x L plasma(-1) x min(-1), respectively; P < 0.002). Obesity was associated with increased VLDL-triacylglycerol secretion in the men (P < 0.001) but not in the women, which resulted in greater rates of VLDL-triacylglycerol secretion in the obese men than in the obese women (6.8 +/- 0.5 and 5.0 +/- 0.5 micro mol x L plasma(-1) x min(-1), respectively; P < 0.05). The clearance of VLDL-triacylglycerol from plasma was greater (P < 0.05) in the lean women than in the lean men (42 +/- 7 and 27 +/- 4 mL plasma/min, respectively) or in the obese men and obese women (28 +/- 3 and 20 +/- 4 mL plasma/min, respectively). The plasma VLDL-triacylglycerol concentration was directly related to the rate of VLDL-triacylglycerol secretion in the men (R(2) = 0.79, P < 0.001) and inversely related to VLDL-triacylglycerol clearance in the women (R(2) = 0.84, P<0.001). Sex and obesity have independent effects on basal VLDL-triacylglycerol kinetics.

Effect of aging on glucose and lipid metabolism during endurance exercise.

Endurance exercise increases the use of endogenous fuels to provide energy for working muscles. Elderly subjects oxidize more glucose and less fat during moderate intensity exercise. This shift in substrate use is presumably caused by age-related changes in skeletal muscle, including decreased skeletal muscle respiratory capacity, because adipose tissue lipolysis and plasma fatty acid availability are not rate limiting. Endurance training in elderly subjects increases muscle respiratory capacity, decreases glucose production and oxidation, and increases fat oxidation thereby correcting or compensating for the alterations in substrate oxidation associated with aging.

Oxidation of nonplasma fatty acids during exercise is increased in women with abdominal obesity.

We evaluated plasma fatty acid availability and plasma and whole body fatty acid oxidation during exercise in five lean and five abdominally obese women (body mass index = 21 +/- 1 vs. 38 +/- 1 kg/m(2)), who were matched on aerobic fitness, to test the hypothesis that obesity alters the relative contribution of plasma and nonplasma fatty acids to total energy production during exercise. Subjects exercised on a recumbent cycle ergometer for 90 min at 54% of their peak oxygen consumption. Stable isotope tracer methods ([(13)C]palmitate) were used to measure fatty acid rate of appearance in plasma and the rate of plasma fatty acid oxidation, and indirect calorimetry was used to measure whole body substrate oxidation. During exercise, palmitate rate of appearance increased progressively and was similar in obese and lean groups between 60 and 90 min of exercise [3.9 +/- 0.4 vs. 4.0 +/- 0.3 micromol. kg fat free mass (FFM)(-1). min(-1)]. The rate of plasma fatty acid oxidation was also similar in obese and lean subjects (12.8 +/- 1.7 vs. 14.5 +/- 1.8 micromol. kg FFM(-1). min(-1); P = not significant). However, whole body fatty acid oxidation during exercise was 25% greater in obese than in lean subjects (21.9 +/- 1.2 vs. 17.5 +/- 1.6 micromol. kg FFM(-1). min(-1); P < 0.05). These results demonstrate that, although plasma fatty acid availability and oxidation are similar during exercise in lean and obese women, women with abdominal obesity use more fat as a fuel by oxidizing more nonplasma fatty acids.