scholarly journals A Multi-Ingredient Formula Ameliorates Exercise-Induced Fatigue by Changing Metabolic Pathways and Increasing Antioxidant Capacity in Mice

Foods ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3120
Author(s):  
Hui Chen ◽  
Xuan Ma ◽  
Lixing Cao ◽  
Shuang Zhao ◽  
Chong Zhao ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Antioxidant Capacity ◽  
Signaling Pathways ◽  
Glucose Transporter ◽  
Adenosine Monophosphate ◽  
Liver Glycogen ◽  
Acid Oxidation ◽  
Isoleucine Leucine ◽  
Improve Exercise Performance ◽  
Exercise Induced

Multiple mechanisms are involved in exercise-induced fatigue, including energy depletion, metabolite accumulation, and oxidative stress, etc. The mechanistic findings provide a rationale for a multi-targeted approach to exercise-induced fatigue management. This study created a multi-ingredient formula mixed with valine, isoleucine, leucine, β-alanine, creatine, l-carnitine, quercetin, and betaine, based on the functional characteristics of these agents, and evaluated the preventive effect of this mechanism-based formula on exercise-induced fatigue. Results showed that the 7-d formula supplement significantly increased the running duration time of mice by 14% and the distance by 20% in an exhaustive treadmill test, indicating that the formula could delay fatigue appearance and improve exercise performance. Mechanistically, the formula enhanced fatty acid oxidation and spared liver glycogen by regulating the fat/glucose metabolism-related signaling pathways, including phospho-adenosine monophosphate-activated protein kinase α (p-AMPKα), phospho-acetyl CoA carboxylase (p-ACC), carnitine palmitoyl-transferase 1B (CPT1B), fatty acid translocase (CD36), and glucose transporter type 4 (GLUT4), and increased antioxidant capacity. The findings suggested that the formula tested in this study effectively ameliorated exercise-induced fatigue by targeting multi-signaling pathways, showing promise as a regimen to fight exercise-induced fatigue.

Effects of the oral hypoglycemic agent methyl palmoxirate on exercise capacity of rats

1984 ◽  
Vol 62 (7) ◽  
pp. 815-818 ◽  
Author(s):  
J. C. Young ◽  
J. E. Bryan ◽  
S. H. Constable ◽  
G. F. Tutwiler ◽  
J. O. Holloszy
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Exercise Capacity ◽  
Liver Glycogen ◽  
Oral Hypoglycemic Agent ◽  
Strenuous Exercise ◽  
Acid Oxidation ◽  
Hypoglycemic Agent ◽  
Minimal Treatment ◽  
Exercise Induced

The effect of the oral hypoglycemic agent methyl palmoxirate (methyl 2-tetradecylglycidate, McN-3716), a selective inhibitor of long chain fatty acid oxidation, on the exercise capacity of normal rats was evaluated. Daily administration of 2.5 mg/kg for 7 days, or of a single dose of 10 mg/kg, of methyl palmoxirate did not affect the ability of rats to perform strenuous exercise of an intensity that caused exhaustion in less than 30 min. The ability to perform prolonged, moderately strenuous exercise of an intensity that could be maintained for more than 60 min was decreased slightly (17%) in the methyl palmoxirate treated rats. This effect appeared to be mediated by a significant reduction in initial liver glycogen content in the methyl palmoxirate treated rats. As a consequence, the methyl palmoxirate treated rats became hypoglycemic during prolonged exercise. Inhibition of fatty acid oxidation in skeletal muscle was minimal. Treatment with methyl palmoxirate protected against the development of exercise-induced ketosis. It appears that the liver is the major site of action of methyl palmoxirate when given in low dosage.

Effects of subbasal insulin infusion on resting and exercise-induced glucose turnover in depancreatized dogs

1993 ◽  
Vol 264 (3) ◽  
pp. E334-E341 ◽  
Author(s):  
Z. Q. Shi ◽  
A. Giacca ◽  
K. Yamatani ◽  
S. J. Fisher ◽  
H. L. Lickley ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Insulin Infusion ◽  
Glucose Turnover ◽  
Acid Oxidation ◽  
Minimal Amount ◽  
Adrenergic Blockade ◽  
Metabolic Clearance ◽  
Diabetic Dogs ◽  
Exercise Induced

beta-Adrenergic blockade suppressed lipolysis and normalized the exercise-induced increments in glucose uptake (GlcU) and metabolic clearance rate (MCR) in alloxan-diabetic dogs with residual insulin, but not in insulin-deprived depancreatized dogs even when combined with methylpalmoxirate (MP), which suppresses fatty acid oxidation. The effects of a minimal amount of insulin (as in the alloxan-diabetic dog), were studied in depancreatized, 24-h insulin-deprived dogs during rest and treadmill exercise (6 km/h, 10% slope) using a 1/4 basal insulin infusion (50 microU.kg-1.min-1, insulin, n = 6) alone, or with MP (20 mg.kg-1.day orally, 2.5 days, MP+insulin, n = 6). At rest, insulin decreased circulating fatty acids (31%) and Glc (13%) and increased GlcU and MCR (86 and 72%). Glc production was unaffected. MP plus insulin markedly suppressed hepatic fatty acid oxidation, decreased Glc (44%) and Glc production (50%), and markedly increased MCR (128%). The exercise-induced increments in MCR were markedly improved only by MP plus insulin but were still lower than in the propranolol-treated alloxan-diabetic dogs. Plasma Glc inversely correlated with the exercise-induced increase in MCR (r = -0.86). We conclude that 1) acute infusion of subbasal insulin improved GlcU in depancreatized dogs at rest but not during exercise; 2) inhibition of fatty acid oxidation combined with subbasal insulin improved the exercise-induced increase in MCR; and 3) the difference in GlcU and MCR between the MP plus insulin-treated depancreatized dogs and the beta-blockade-treated alloxan-diabetic dogs suggests a difference between acute and chronic effects of insulin.

scholarly journals d-allulose Ameliorates Metabolic Dysfunction in C57BL/KsJ-db/db Mice

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3656
Author(s):  
Dayoun Lee ◽  
Youngji Han ◽  
Eun-Young Kwon ◽  
Myung-Sook Choi
Keyword(s):  
Fatty Acid ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Glucose Transporter ◽  
Inflammatory Responses ◽  
Normal Diet ◽  
Acid Oxidation ◽  
Transferase Activity ◽  
Model Assessment ◽  
Hepatic Fatty Acid

d-allulose is an uncommon sugar that provides almost no calories when consumed. Its sweetness is 70% that of sucrose. d-allulose is a metabolic regulator of glucose and lipid metabolism. However, few reports concerning its effect on diabetes and related metabolic disturbances in db/db mice are available. In this study, we evaluated d-allulose’s effect on hyperglycemia, hyperinsulinemia, diabetes and inflammatory responses in C57BL/KsJ-db/db mice. Mice were divided into normal diet, erythritol supplemented (5% w/w), and d-allulose supplemented (5% w/w) groups. Blood glucose and plasma glucagon levels and homeostatic model assessment (HOMA-IR) were significantly lower in the d-allulose group than in the normal diet group, and plasma insulin level was significantly increased. Further, d-allulose supplement significantly increased hepatic glucokinase activity and decreased hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activity. Expression of glucose transporter 4, insulin receptor substrate 1, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha and AKT serine/threonine kinase 2 were also upregulated by d-allulose supplement in adipocyte and muscle. Finally, d-allulose effectively lowered plasma and hepatic triglyceride and free fatty acid levels, and simultaneously reduced hepatic fatty acid oxidation and carnitine palmitoyl transferase activity. These changes are likely attributable to suppression of hepatic fatty acid synthase and glucose-6-phosphate dehydrogenase activity. Notably, d-allulose also reduced pro-inflammatory adipokine and cytokine levels in plasma. Our results indicate that d-allulose is an effective sugar substitute for improving lipid and glucose metabolism.

Excess body fat in men decreases plasma fatty acid availability and oxidation during endurance exercise

2004 ◽  
Vol 286 (3) ◽  
pp. E354-E362 ◽  
Author(s):  
Bettina Mittendorfer ◽  
David A. Fields ◽  
Samuel Klein
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Body Fat ◽  
Fat Mass ◽  
Total Fatty Acid ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Plasma Fatty Acids ◽  
Exercise Induced

The effect of relative body fat mass on exercise-induced stimulation of lipolysis and fatty acid oxidation was evaluated in 15 untrained men (5 lean, 5 overweight, and 5 obese with body mass indexes of 21 ± 1, 27 ± 1, and 34 ± 1 kg/m2, respectively, and %body fat ranging from 12 to 32%). Palmitate and glycerol kinetics and substrate oxidation were assessed during 90 min of cycling at 50% peak aerobic capacity (V̇o2 peak) by use of stable isotope-labeled tracer infusion and indirect calorimetry. An inverse relationship was found between %body fat and exercise-induced increase in glycerol appearance rate relative to fat mass ( r2 = 0.74; P < 0.01). The increase in total fatty acid uptake during exercise [(μmol/kg fat-free mass) × 90 min] was ∼50% smaller in obese (181 ± 70; P < 0.05) and ∼35% smaller in overweight (230 ± 71; P < 0.05) than in lean (354 ± 34) men. The percentage of total fatty acid oxidation derived from systemic plasma fatty acids decreased with increasing body fat, from 49 ± 3% in lean to 39 ± 4% in obese men ( P < 0.05); conversely, the percentage of nonsystemic fatty acids, presumably derived from intramuscular and possibly plasma triglycerides, increased with increasing body fat ( P < 0.05). We conclude that the lipolytic response to exercise decreases with increasing adiposity. The blunted increase in lipolytic rate in overweight and obese men compared with lean men limits the availability of plasma fatty acids as a fuel during exercise. However, the rate of total fat oxidation was similar in all groups because of a compensatory increase in the oxidation of nonsystemic fatty acids.

Effect of adrenodemedullation on decline in muscle malonyl-CoA during exercise

1993 ◽  
Vol 74 (5) ◽  
pp. 2548-2551 ◽  
Author(s):  
W. W. Winder ◽  
R. W. Braiden ◽  
D. C. Cartmill ◽  
C. A. Hutber ◽  
J. P. Jones
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Treadmill Running ◽  
Acid Oxidation ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Malonyl Coa ◽  
Exercise Induced ◽  
Rate Limiting

Malonyl-CoA is an inhibitor of carnitine palmitoyltransferase, a rate-limiting enzyme of fatty acid oxidation. Previous studies have indicated that muscle malonyl-CoA declines in rats during treadmill running. This decrease may be important for allowing an increased rate of fatty acid oxidation during prolonged exercise. This study was designed to determine whether epinephrine is essential for inducing the decline in muscle malonyl-CoA during exercise. Male Sprague-Dawley rats underwent adrenodemedullation (ADM) or sham operation. After allowing 3 wk for recovery, rats were killed (pentobarbital anesthesia) at rest or after running at 21 m/min up a 15% grade for 60 min. Red quadriceps malonyl-CoA decreased from 2.6 +/- 0.3 to 0.8 +/- 0.07 nmol/g in sham-operated rats and from 2.2 +/- 0.3 to 0.8 +/- 0.1 nmol/g in ADM rats. White quadriceps malonyl-CoA decreased to similar levels during exercise in both sham-operated and ADM rats. A second experiment on 24-h fasted rats also showed no impairment in the exercise-induced decline in red quadriceps malonyl-CoA as a result of adrenodemedullation. The hormones of the adrenal medulla are therefore unessential for inducing the decline in malonyl-CoA during exercise.

Muscle malonyl-CoA decreases during exercise

1989 ◽  
Vol 67 (6) ◽  
pp. 2230-2233 ◽  
Author(s):  
W. W. Winder ◽  
J. Arogyasami ◽  
R. J. Barton ◽  
I. M. Elayan ◽  
P. R. Vehrs
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Plasma Catecholamines ◽  
Male Rats ◽  
Acid Oxidation ◽  
Glycogen Depletion ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa ◽  
Important Regulator ◽  
Exercise Induced

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.

scholarly journals The role of hepatocellular eNOS in NAFLD development and hepatic mitochondrial adaptations to exercise

2020 ◽  
Author(s):  
◽  
Rory P. Cunningham
Keyword(s):  
Nitric Oxide ◽  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Fatty Acid Oxidation ◽  
Whole Body ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Exercise Induced ◽  
Mitochondrial Adaptations

Whole body loss of endothelial nitric oxide synthase (eNOS) worsens hepatic mitochondrial function and exacerbates nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) development and progression. However, the precise role of eNOS in hepatocytes in the contribution to NAFLD has not been established. Here, we use gain- and loss- of-function approaches including a hepatocyte-specific eNOS knockout mouse model (eNOShep-/-), and lifestyle interventions (diet and exercise), to investigate the role of hepatocellular eNOS in NAFLD/NASH development and hepatic mitochondrial adaptations to exercise. Ablation of hepatocellular eNOS via genetic and viral knockout exacerbated hepatic steatosis and inflammation, decreased hepatic mitochondrial fatty acid oxidation and respiration, and impaired mitophagy. Conversely, overexpressing hepatocellular eNOS via viral approaches increased hepatocyte respiration, markers of mitophagy, while attenuating NASH progression. Interestingly, these detriments were not rescued by BNIP3 overexpression or nitric oxide (NO) donors in eNOS deficient hepatocytes. In addition, elevated H2O2 emission and hepatic steatosis in eNOShep-/- mice was completely ablated with 10 weeks of voluntary wheel running exercise. Interestingly, eNOShep-/- male mice had a blunted exercise-induced increase in hepatic fatty acid oxidation. eNOShep-/- mice also had impaired markers of energy sensing ability of the cell and attenuated activation of the autophagy initiating factor ULK1. While mitochondrial respiration and markers of mitochondrial content were not increased with exercise, female mice showed markers of mitochondrial biogenesis. Collectively, these data uncover the important and novel role of hepatocellular eNOS in exercise-induced hepatic mitochondrial adaptations, and help to further the understanding behind the mechanistic role of eNOS in NAFLD development.

Exercise, FGF21, and PGC-1 : roles in hepatic metabolism

2014 ◽  
Author(s):  
◽  
Justin Andrew Fletcher
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Gene Transcription ◽  
Fibroblast Growth Factor 21 ◽  
Acid Oxidation ◽  
Wild Type ◽  
Hepatic Fatty Acid ◽  
Exercise Induced ◽  
Hepatic Fatty Acid Oxidation ◽  
Mitochondrial Adaptations

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The liver is instrumental in maintaining euglycemia during times of fasting and exercise, and in-turn exercise is a stimulus that challenges the liver and results in hepatic mitochondrial adaptations. Mechanisms responsible for these improvements in mitochondrial function are not currently known. Fibroblast growth factor 21 (FGF21), a powerful metabolic regulator, is one potential mechanism responsible for exercise- induced hepatic mitochondrial adaptations. Previous studies show that FGF21 modulates hepatic fatty acid oxidation (FAO), gluconeogenesis, ketogenesis, and TCA cycle flux, in addition to gene transcription of proteins important to these processes. The purpose of the first objective in the current study was to examine whether FGF21 is necessary for exercise to induce hepatic mitochondrial adaptations in mice. A second objective was to determine if PGC--1? is responsible for the upregulation of genes important to metabolic processes in response to FGF21 signaling. We mechanistically assessed the necessity of FGF21 for exercise-induced hepatic mitochondrial adaptations by providing wild-type and FGF21 knockout mice with running wheels for 8 weeks to promote physical activity. A major finding in the current study is that the FGF21KO mice experience a hepatic fatty acid oxidation deficit compared to the wild-type group and that 8 weeks of voluntary wheel running normalized FAO in the FGF21KO mice. The role of PGC-1[alpha] in FGF21 regulation of gene transcription was also assessed by continuously administering FGF21 (1 mg/kg), or saline into wild-type or liver specific PGC--1[alpha] heterozygous mice (LPGC--1[alpha]) for 4 weeks. It was found that female mice did not express a phenotype effect; however, in male mice hepatic FAO was significantly blunted in the LPGC-1[alpha] mice, yet FGF21 administration was able to elevate FAO regardless in both genotypes. Collectively, this data suggests that FGF21 is necessary for the expression and content of certain genes or proteins, but that VWR is able to circumvent the absence of FGF21 and normalize hepatic FAO. Furthermore, a reduction in hepatic PGC-1[alpha] does not appear to influence the ability of FGF21 to regulate hepatic FAO.

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