Effects of reduced free fatty acid availability on hormone-sensitive lipase activity in human skeletal muscle during aerobic exercise

2004 ◽  
Vol 97 (5) ◽  
pp. 1938-1945 ◽  
Author(s):  
Marcus O'Neill ◽  
Matthew J. Watt ◽  
George J. F. Heigenhauser ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Aerobic Exercise ◽  
Fat Oxidation ◽  
Dry Mass ◽  
Hormone Sensitive Lipase ◽  
Hormone Sensitive ◽  
Plasma Ffa ◽  
Muscle Biopsies

Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of intramuscular triacylglycerol (IMTG); however, its regulation in skeletal muscle is poorly understood. To examine the effects of reduced free fatty acid (FFA) availability on HSL activity in skeletal muscle during aerobic exercise, 11 trained men exercised at 55% maximal O2 uptake for 40 min after the ingestion of nicotinic acid (NA) or nothing (control). Muscle biopsies were taken at rest and 5, 20, and 40 min of exercise. Plasma FFA were suppressed ( P < 0.05) in NA during exercise (∼0.40 ± 0.04 vs. ∼0.07 ± 0.01 mM). The respiratory exchange ratio (RER) was increased throughout exercise (0.020 + 0.008) after NA ingestion. However, the provision of energy from fat oxidation only decreased from 33% of the total in the control trial to 26% in the NA trial, suggesting increased IMTG oxidation in the NA trial. Mean HSL activity was 2.25 + 0.15 mmol·kg dry mass−1·min−1 at rest and increased ( P < 0.05) to 2.94 ± 0.20 mmol·kg dry mass−1·min−1 at 5 min in control. Contrary to the hypothesis, mean HSL was not activated to a greater extent in the NA trial during exercise (2.20 + 0.28 at rest to 2.88 + 0.21 mmol·kg dry mass−1·min−1 at 5 min). No further HSL increases were observed at 20 or 40 min in both trials. There was variability in the response to NA ingestion, as some subjects experienced a large increase in RER and decrease in fat oxidation, whereas other subjects experienced no shift in RER and maintained fat oxidation despite the reduced FFA availability in the NA trial. However, even in these subjects, HSL activity was not further increased during the NA trial. In conclusion, reduced plasma FFA availability accompanied by increased epinephrine concentration did not further activate HSL beyond exercise alone.

Reduced plasma FFA availability increases net triacylglycerol degradation, but not GPAT or HSL activity, in human skeletal muscle

2004 ◽  
Vol 287 (1) ◽  
pp. E120-E127 ◽  
Author(s):  
Matthew J. Watt ◽  
Anna G. Holmes ◽  
Gregory R. Steinberg ◽  
Jose L. Mesa ◽  
Bruce E. Kemp ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Body Fat ◽  
Plasma Free Fatty Acid ◽  
Fat Oxidation ◽  
Dry Mass ◽  
Hormone Sensitive Lipase ◽  
Whole Body ◽  
Plasma Ffa

Intramuscular triacylglycerols (IMTG) are proposed to be an important metabolic substrate for contracting muscle, although this remains controversial. To test the hypothesis that reduced plasma free fatty acid (FFA) availability would increase IMTG degradation during exercise, seven active men cycled for 180 min at 60% peak pulmonary O2 uptake either without (CON) or with (NA) prior ingestion of nicotinic acid to suppress adipose tissue lipolysis. Skeletal muscle and adipose tissue biopsy samples were obtained before and at 90 and 180 min of exercise. NA ingestion decreased ( P < 0.05) plasma FFA at rest and completely suppressed the exercise-induced increase in plasma FFA (180 min: CON, 1.42 ± 0.07; NA, 0.10 ± 0.01 mM). The decreased plasma FFA during NA was associated with decreased ( P < 0.05) adipose tissue hormone-sensitive lipase (HSL) activity (CON: 13.9 ± 2.5, NA: 9.1 ± 3.0 nmol·min−1·mg protein−1). NA ingestion resulted in decreased whole body fat oxidation and increased carbohydrate oxidation. Despite the decreased whole body fat oxidation, net IMTG degradation was greater in NA compared with CON (net change: CON, 2.3 ± 0.8; NA, 6.3 ± 1.2 mmol/kg dry mass). The increased IMTG degradation did not appear to be due to reduced fatty acid esterification, because glycerol 3-phosphate activity was not different between trials and was unaffected by exercise (rest: 0.21 ± 0.07; 180 min: 0.17 ± 0.04 nmol·min−1·mg protein−1). HSL activity was not increased from resting rates during exercise in either trial despite elevated plasma epinephrine, decreased plasma insulin, and increased ERK1/2 phosphorylation. AMP-activated protein kinase (AMPK)α1 activity was not affected by exercise or NA, whereas AMPKα2 activity was increased ( P < 0.05) from rest during exercise in NA and was greater ( P < 0.05) than in CON at 180 min. These data suggest that plasma FFA availability is an important mediator of net IMTG degradation, and in the absence of plasma FFA, IMTG degradation cannot maintain total fat oxidation. These changes in IMTG degradation appear to disassociate, however, from the activity of the key enzymes responsible for synthesis and degradation of this substrate.

Impaired plasma FFA oxidation imposed by extreme CHO deficiency in contracting rat skeletal muscle

1994 ◽  
Vol 77 (2) ◽  
pp. 517-525 ◽  
Author(s):  
L. P. Turcotte ◽  
P. J. Hespel ◽  
T. E. Graham ◽  
E. A. Richter
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Uptake ◽  
Swimming Exercise ◽  
Rat Skeletal Muscle ◽  
Palmitate Oxidation ◽  
Plasma Ffa ◽  
Ffa Metabolism ◽  
Palmitate Uptake

The extent to which carbohydrate (CHO) availability affects free fatty acid (FFA) metabolism in contracting skeletal muscle is not well characterized. To study this question, rats were depleted of glycogen by swimming exercise and lard feeding 24 h before perfusion of their isolated hindquarters. After 20 min of preperfusion with a medium containing no glucose, palmitate (600 or 2,000 microM), and [1–14C]palmitate, flow was restricted to one hindlimb, which was electrically stimulated for 2 min to further deplete muscles of glycogen. After 2 min of recovery, glucose was added to the perfusate at final concentrations of 0, 6, or 20 mM, and after another 3 min muscles were stimulated for 30 min. At 6 and 2,000 microM palmitate, glucose uptake after 30 min of stimulation averaged 23.5 +/- 9.3 and 45.9 +/- 10.6 mumol.g-1.h-1 with 6 and 20 mM glucose, respectively. At 6 and 2,000 microM palmitate, palmitate uptake was lower (30–37%, P < 0.05) with 0 than with 6 or 20 mM glucose. At 600 microM palmitate, percent palmitate oxidation was higher (27%, P < 0.05) with 0 than with 6 or 20 mM glucose, resulting in similar total palmitate oxidation with the three glucose concentrations (0.28 +/- 0.01 mumol.g-1.h-1). At 2,000 microM palmitate, percent palmitate oxidation was not significantly different among glucose concentrations, resulting in a significantly lower rate of palmitate oxidation with 0 (0.62 +/- 0.18 mumol.g-1.h-1) than with 6 or 20 mM glucose (0.77 +/- 0.25 and 0.78 +/- 0.20 mumol.g-1.h-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of reduced free fatty acid availability on skeletal muscle PDH activation during aerobic exercise

2003 ◽  
Vol 284 (3) ◽  
pp. E589-E596 ◽  
Author(s):  
Trent Stellingwerff ◽  
Matthew J. Watt ◽  
G. J. F. Heigenhauser ◽  
Lawrence L. Spriet
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Aerobic Exercise ◽  
Statistical Significance ◽  
Carbohydrate Oxidation ◽  
Exercise Onset ◽  
Expired Gas ◽  
Plasma Ffa ◽  
Gas Measurements ◽  
Male Subjects

This study investigated the effect of reduced free fatty acid (FFA) availability on pyruvate dehydrogenase activation (PDHa) and carbohydrate metabolism during moderate aerobic exercise. Eight active male subjects cycled for 40 min at 55% V˙o 2 peak on two occasions. During one trial, subjects ingested 20 mg/kg body mass of the antilipolytic drug nicotinic acid (NA) during the hour before exercise to reduce FFA. Nothing was ingested in the control trial (CON). Blood and expired gas measurements were obtained throughout the trials, and muscle biopsy samples were obtained immediately before exercise and at 5, 20, and 40 min of exercise. Plasma FFA were lower in the NA trial (0.13 ± 0.01 vs. 0.48 ± 0.03 mM, P < 0.05), and the respiratory exchange ratio (RER) was increased with NA (0.93 ± 0.01 vs. 0.89 ± 0.01, P < 0.05), resulting in a 14.5 ± 1.8% increase in carbohydrate oxidation compared with CON. PDHa increased rapidly in both trials at exercise onset but was ∼15% higher ( P < 0.05) throughout exercise in the NA trial (2.44 ± 0.19 and 2.07 ± 0.12 mmol · kg wet muscle−1 · min−1 for NA and CON at 40 min). Muscle glycogenolysis was 15.3 ± 9.6% greater in the NA trial vs. the CON trial but did not reach statistical significance. Glucose 6-phosphate contents were elevated ( P < 0.05) in the NA trial at 30 and 40 min of exercise, but pyruvate and lactate contents were unaffected. These data demonstrate that the reduction of exogenous FFA availability increased the activation of PDH and carbohydrate oxidation during moderate aerobic exercise in men. The increased activation of PDH was not explained by changes in muscle pyruvate or the ATP/ADP ratio but may be related to a decrease in the NADH/NAD+ ratio or an epinephrine-induced increase in calcium concentration.

scholarly journals Plasma free fatty acid concentration is closely tied to whole body peak fat oxidation rate during repeated exercise

2019 ◽  
Vol 126 (6) ◽  
pp. 1563-1571 ◽  
Author(s):  
Jacob Frandsen ◽  
Stine Dahl Vest ◽  
Christian Ritz ◽  
Steen Larsen ◽  
Flemming Dela ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Body Fat ◽  
Oxidation Rate ◽  
Plasma Free Fatty Acid ◽  
Fat Oxidation ◽  
Whole Body ◽  
Exercise Tests ◽  
Repeated Exercise ◽  
Plasma Ffa

Plasma free fatty acids (FFA) are a major contributor to whole body fat oxidation during exercise. However, the extent to which manipulating plasma FFA concentrations will influence whole body peak fat oxidation rate (PFO) during exercise remains elusive. In this study we aimed to increase plasma FFA concentrations through a combination of fasting and repeated exercise bouts. We hypothesized that an increase in plasma FFA concentration would increase PFO in a dose-dependent manner. Ten healthy young (31 ± 6 yr) (mean ± SD) well-trained (maximal oxygen uptake 65.9 ± 6.1 ml·min−1·kg−1) men performed four graded exercise tests (GXTs) on 1 day. The GXTs were interspersed by 4 h of bed rest. This was conducted either in a fasted state or with the consumption of a standardized carbohydrate-rich meal 3.5 h before each GXT. Fasting and previous GXTs resulted in a gradual increase in PFO from 0.63 ± 0.18 g/min after an overnight fast (10 h) to 0.93 ± 0.17 g/min after ∼22 h of fasting and three previous GXTs. This increase in PFO coincided with an increase in plasma FFA concentrations ( r2 = 0.73, P < 0.0001). Ingestion of a carbohydrate-rich meal 3.5 h before each GXT resulted in unaltered PFO. This was also reflected in unchanged plasma FFA, glucose, and insulin concentrations. In this study we show that plasma FFA availability is closely tied to whole body PFO and that the length of fasting combined with previous exercise are robust stimuli toward increasing plasma FFA concentration, highlighting the importance for preexercise standardization when conducting GXTs measuring substrate oxidation. NEW & NOTEWORTHY We show that peak fat oxidation is increased in close relationship with plasma free fatty acid availability after combined fasting and repeated incremental exercise tests in healthy highly trained men. Therefore it may be argued that whole body fat oxidation rate measured in most cases after an overnight fast indeed does not represent whole body maximal fat oxidation rate but a whole body peak fat oxidation rate within the context of the preexercise standardization obtained in the study design.

scholarly journals Peak Fat Oxidation Rate Is Closely Associated With Plasma Free Fatty Acid Concentrations in Women; Similar to Men

2021 ◽  
Vol 12 ◽  
Author(s):  
Jacob Frandsen ◽  
Axel Illeris Poggi ◽  
Christian Ritz ◽  
Steen Larsen ◽  
Flemming Dela ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Plasma Free Fatty Acid ◽  
Fat Oxidation ◽  
Whole Body ◽  
Men And Women ◽  
Fed State ◽  
Repeated Exercise ◽  
Graded Exercise ◽  
Plasma Ffa

Introduction: In men, whole body peak fat oxidation (PFO) determined by a graded exercise test is closely tied to plasma free fatty acid (FFA) availability. Men and women exhibit divergent metabolic responses to fasting and exercise, and it remains unknown how the combined fasting and exercise affect substrate utilization in women. We aimed to investigate this, hypothesizing that increased plasma FFA concentrations in women caused by fasting and repeated exercise will increase PFO during exercise. Then, that PFO would be higher in women compared with men (data from a previous study).Methods: On two separate days, 11 young endurance-trained women were investigated, either after an overnight fast (Fast) or 3.5 h after a standardized meal (Fed). On each day, a validated graded exercise protocol (GXT), used to establish PFO by indirect calorimetry, was performed four times separated by 3.5 h of bed rest both in the fasted (Fast) or fed (Fed) state.Results: Peak fat oxidation increased in the fasted state from 11 ± 3 (after an overnight fast, Fast 1) to 16 ± 3 (mean ± SD) mg/min/kg lean body mass (LBM) (after ~22 h fast, Fast 4), and this was highly associated with plasma FFA concentrations, which increased from 404 ± 203 (Fast 1) to 865 ± 210 μmol/L (Fast 4). No increase in PFO was found during the fed condition with repeated exercise. Compared with trained men from a former identical study, we found no sex differences in relative PFO (mg/min/kg LBM) between men and women, in spite of significant differences in plasma FFA concentrations during exercise after fasting.Conclusion: Peak fat oxidation increased with fasting and repeated exercise in trained women, but the relative PFO was similar in young trained men and women, despite major differences in plasma lipid concentrations during graded exercise.

EFFECTS OF REDUCED FREE FATTY ACID AVAILABILITY ON SKELETAL MUSCLE PDH ACTIVATION DURING AEROBIC EXERCISE

2003 ◽  
Vol 35 (Supplement 1) ◽  
pp. S147
Author(s):  
T Stellingwerff ◽  
M J. Watt ◽  
G J.F. Heigenhauser ◽  
L L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Aerobic Exercise

Hormone-sensitive lipase activity and fatty acyl-CoA content in human skeletal muscle during prolonged exercise

2003 ◽  
Vol 95 (1) ◽  
pp. 314-321 ◽  
Author(s):  
Matthew J. Watt ◽  
George J. F. Heigenhauser ◽  
Marcus O'Neill ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Prolonged Exercise ◽  
Dry Mass ◽  
Fatty Acyl ◽  
Hormone Sensitive Lipase ◽  
Inhibitory Effects ◽  
Hormone Sensitive ◽  
Hydrolysis Of ◽  
Long Chain

Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of intramuscular triacylglycerols (IMTGs), but HSL regulation is poorly understood in skeletal muscle. The present study measured human skeletal muscle HSL activity at rest and during 120 min of cycling at 60% of peak O2 uptake. Several putative HSL regulators were also measured, including muscle long-chain fatty acyl-CoA (LCFA CoA) and free AMP contents and plasma epinephrine and insulin concentrations. HSL activity increased from resting levels by 10 min of exercise (from 2.09 ± 0.19 to 2.56 ± 0.22 mmol · min-1 · kg dry mass-1, P < 0.05), increased further by 60 min (to 3.12 ± 0.27 mmol · min-1 · kg dry mass-1, P < 0.05), and decreased to near-resting rates after 120 min of cycling. Skeletal muscle LCFA CoA increased ( P < 0.05) above rest by 60 min (from 15.9 ± 3.0 to 50.4 ± 7.9 μmol/kg dry mass) and increased further by 120 min. Estimated free AMP increased ( P < 0.05) from rest to 60 min and was ∼20-fold greater than that at rest by 120 min. Epinephrine was increased above rest ( P < 0.05) at 60 (1.47 ± 0.15 nM) and 120 min (4.87 ± 0.76 nM) of exercise. Insulin concentrations decreased rapidly and were lower than resting levels by 10 min and continued to decrease throughout exercise. In summary, HSL activity was increased from resting levels by 10 min, increased further by 60 min, and decreased to near-resting values by 120 min. The increased HSL activity at 60 min was associated with the stimulating effect of increased epinephrine and decreased insulin levels. After 120 min, the decreased HSL activity was associated with the proposed inhibitory effects of increased free AMP. The accumulation of LCFA CoA in the 2nd h of exercise may also have reduced the flux through HSL and accounted for the reduction in IMTG utilization previously observed late in prolonged exercise.

scholarly journals Central melanocortin stimulation increases phosphorylated perilipin A and hormone-sensitive lipase in adipose tissues

2010 ◽  
Vol 299 (1) ◽  
pp. R140-R149 ◽  
Author(s):  
Y. B. Shrestha ◽  
C. H. Vaughan ◽  
B. J. Smith ◽  
C. K. Song ◽  
D. J. Baro ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Sympathetic Nerves ◽  
Hormone Sensitive Lipase ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Perilipin A ◽  
Hormone Sensitive

Norepinephrine (NE) released from the sympathetic nerves innervating white adipose tissue (WAT) is the principal initiator of lipolysis in mammals. Central WAT sympathetic outflow neurons express melanocortin 4-receptor (MC4-R) mRNA. Single central injection of melanotan II (MTII; MC3/4-R agonist) nonuniformly increases WAT NE turnover (NETO), increases interscapular brown adipose tissue (IBAT) NETO, and increases the circulating lipolytic products glycerol and free fatty acid. The WAT pads that contributed to this lipolysis were inferred from the increases in NETO. Because phosphorylation of perilipin A (p-perilipin A) and hormone-sensitive lipase are necessary for NE-triggered lipolysis, we tested whether MTII would increase these intracellular markers of lipolysis. Male Siberian hamsters received a single 3rd ventricular injection of MTII or saline. Trunk blood was collected at 0.5, 1.0, and 2.0 h postinjection from excised inguinal, retroperitoneal, and epididymal WAT (IWAT, RWAT, and EWAT, respectively) and IBAT pads. MTII increased circulating glycerol concentrations at 0.5 and 1.0 h, whereas free fatty acid concentrations were increased at 1.0 and 2.0 h. Western blot analysis showed that MTII specifically increased p-perilipin A and hormone-sensitive lipase only in fat pads that previously had MTII-induced increases in NETO. Phosphorylation increased in IWAT at all time points and IBAT at 0.5 h, but not RWAT or EWAT at any time point. These results show for the first time in rodents that p-perilipin A can serve as an in vivo, fat pad-specific indictor of lipolysis and extend our previous findings showing that central melanocortin stimulation increases WAT lipolysis.

Effect of exercise on FFA metabolism of pancreatectomized dogs

1963 ◽  
Vol 205 (4) ◽  
pp. 645-650 ◽  
Author(s):  
B. Issekutz ◽  
H. I. Miller ◽  
K. Rodahl
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Specific Activity ◽  
Plasma Free Fatty Acid ◽  
Fat Oxidation ◽  
Striking Difference ◽  
Heavy Exercise ◽  
Plasma Ffa ◽  
Ffa Metabolism ◽  
Pancreatectomized Dogs

Normal and pancreatectomized dogs with indwelling arterial and venous catheters were exercised on the treadmill for 35 min. Palmitate-1-C14 was infused intravenously for 3 hr during the experiment, or administered orally 15 hr before the experiment. The plasma free fatty acid (FFA) level was decreased in normal dogs but increased in the pancreatectomized animals during exercise. This was due to corresponding changes in the rate of FFA release. The rate of uptake of plasma FFA followed the rate of release with some delay, so that at the end of exercise the uptake was tenfold higher in the pancreatectomized dogs than in the controls. In spite of this striking difference, the C14O2 output was increased during exercise four- to fivefold in both groups in the infusion experiments. When the radiopalmitate was administered orally, however, the specific activity of the exhaled C14O2 rapidly decreased in the exercising pancreatectomized dogs but remained rather constant in the controls. It is suggested that during heavy exercise the muscles of the normal dog oxidize their endogenous fat pools, whereas the pancreatectomized animal relies for fat oxidation on the plasma FFA, the concentration of which is considerably increased by norepinephrine in the absence of insulin.

Glucose ingestion blunts hormone-sensitive lipase activity in contracting human skeletal muscle

2004 ◽  
Vol 286 (1) ◽  
pp. E144-E150 ◽  
Author(s):  
Matthew J. Watt ◽  
Peter Krustrup ◽  
Niels H. Secher ◽  
Bengt Saltin ◽  
Bente K. Pedersen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipase Activity ◽  
Femoral Vein ◽  
Dry Mass ◽  
Hormone Sensitive Lipase ◽  
Arterial Blood ◽  
Carbohydrate Feeding ◽  
Glucose Ingestion ◽  
Hormone Sensitive ◽  
Exercise Muscle

To examine the effect of attenuated epinephrine and elevated insulin on intramuscular hormone sensitivity lipase activity (HSLa) during exercise, seven men performed 120 min of semirecumbent cycling (60% peak pulmonary oxygen uptake) on two occasions while ingesting either 250 ml of a 6.4% carbohydrate (GLU) or sweet placebo (CON) beverage at the onset of, and at 15 min intervals throughout, exercise. Muscle biopsies obtained before and immediately after exercise were analyzed for HSLa. Blood samples were simultaneously obtained from a brachial artery and a femoral vein before and during exercise, and leg blood flow was measured by thermodilution in the femoral vein. Net leg glycerol and lactate release and net leg glucose and free fatty acid (FFA) uptake were calculated from these measures. Insulin and epinephrine were also measured in arterial blood before and throughout exercise. During GLU, insulin was elevated (120 min: CON, 11.4 ± 2.4, GLU, 35.3 ± 6.9 pM, P < 0.05) and epinephrine suppressed (120 min: CON, 6.1 ± 2.5, GLU, 2.1 ± 0.9 nM; P < 0.05) compared with CON. Carbohydrate feeding also resulted in suppressed ( P < 0.05) HSLa relative to CON (120 min: CON, 1.71 ± 0.18, GLU, 1.27 ± 0.16 mmol·min-1·kg dry mass-1). There were no differences in leg lactate or glycerol release when trials were compared, but leg FFA uptake was lower (120 min: CON, 0.29 ± 0.06, GLU, 0.82 ± 0.09 mmol/min) and leg glucose uptake higher (120 min: CON, 3.16 ± 0.59, GLU, 1.37 ± 0.37 mmol/min) in GLU compared with CON. These results demonstrate that circulating insulin and epinephrine play a role in HSLa in contracting skeletal muscle.

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