Transforming growth factor-β in the brain regulates fat metabolism during endurance exercise

2006 ◽  
Vol 291 (6) ◽  
pp. E1151-E1159 ◽  
Author(s):  
Toma Ishikawa ◽  
Wataru Mizunoya ◽  
Tetsuro Shibakusa ◽  
Kazuo Inoue ◽  
Tohru Fushiki
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Transforming Growth Factor ◽  
Plasma Concentrations ◽  
Transforming Growth Factor Β ◽  
Gas Analysis ◽  
Treadmill Running ◽  
Control Group ◽  
Acid Oxidation ◽  
The Brain

We have previously reported that the concentration of transforming growth factor-β (TGF-β) increases in the cerebrospinal fluid of rats during exercise and that there is an increase in whole body fat oxidation following the intracisternal administration of TGF-β. These results led us to postulate that TGF-β in the brain regulates the enhancement of fatty acid oxidation during exercise. To test this hypothesis, we carried out respiratory gas analysis during treadmill running following the inhibition of TGF-β activity in rat brain by intracisternal administration of anti-TGF-β antibody or SB-431542, an inhibitor of the type 1 TGF-β receptor. We found that each reagent partially blocked the increase in the fatty acid oxidation. We also compared the plasma concentrations of energy substrates in the group administered anti-TGF-β antibody and the control group during running. We found that the plasma concentrations of nonesterified fatty acids and ketone bodies in the group administered anti-TGF-β antibody were lower than in the control group at the end of running. In the same way, we carried out respiratory gas analysis during treadmill running after depressing corticotropin-releasing factor activity in the brain using intracisternal administration of astressin, an inhibitor of the corticotropin-releasing factor receptor. However, there were no significant differences in respiratory exchange ratio or oxygen consumption in moderate running (60% maximum oxygen consumption). These results suggest that brain TGF-β has a role in enhancing fatty acid oxidation during endurance exercise and that this regulation is executed at least partly via the type 1 TGF-β receptor signal transduction system.

scholarly journals A Low-Carbohydrate Ketogenic Diet and Treadmill Training Enhanced Fatty Acid Oxidation Capacity but Did Not Enhance Maximal Exercise Capacity in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 611
Author(s):  
Sihui Ma ◽  
Jiao Yang ◽  
Takaki Tominaga ◽  
Chunhong Liu ◽  
Katsuhiko Suzuki
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Exercise Capacity ◽  
Ketogenic Diet ◽  
Maximal Exercise ◽  
Treadmill Running ◽  
Acid Oxidation ◽  
Oxidation Capacity ◽  
Low Carbohydrate ◽  
Maximal Exercise Capacity

The low-carbohydrate ketogenic diet (LCKD) is a dietary approach characterized by the intake of high amounts of fat, a balanced amount of protein, and low carbohydrates, which is insufficient for metabolic demands. Previous studies have shown that an LCKD alone may contribute to fatty acid oxidation capacity, along with endurance. In the present study, we combined a 10-week LCKD with an 8-week forced treadmill running program to determine whether training in conjunction with LCKD enhanced fatty acid oxidation capacity, as well as whether the maximal exercise capacity would be affected by an LCKD or training in a mice model. We found that the lipid pool and fatty acid oxidation capacity were both enhanced following the 10-week LCKD. Further, key fatty acid oxidation related genes were upregulated. In contrast, the 8-week training regimen had no effect on fatty acid and ketone body oxidation. Key genes involved in carbohydrate utilization were downregulated in the LCKD groups. However, the improved fatty acid oxidation capacity did not translate into an enhanced maximal exercise capacity. In summary, while favoring the fatty acid oxidation system, an LCKD, alone or combined with training, had no beneficial effects in our intensive exercise-evaluation model. Therefore, an LCKD may be promising to improve endurance in low- to moderate-intensity exercise, and may not be an optimal choice for those partaking in high-intensity exercise.

Higher mitochondrial fatty acid oxidation following intermittent versus continuous endurance exercise training

1998 ◽  
Vol 76 (9) ◽  
pp. 891-894 ◽  
Author(s):  
P D Chilibeck ◽  
G J Bell ◽  
R P Farrar ◽  
T P Martin
Keyword(s):  
Fatty Acid ◽  
Exercise Training ◽  
Fatty Acid Oxidation ◽  
Endurance Exercise ◽  
High Intensity ◽  
Treadmill Running ◽  
Acid Oxidation ◽  
Interval Exercise ◽  
Endurance Exercise Training ◽  
Mitochondrial Fatty Acid

It has been well documented that skeletal muscle fatty acid oxidation can be elevated by continuous endurance exercise training. However, it remains questionable whether similar adaptations can be induced with intermittent interval exercise training. This study was undertaken to directly compare the rates of fatty acid oxidation in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria following these different exercise training regimes. Mitochondria were isolated from the gastrocnemius-plantaris muscles of male Sprague-Dawley rats following exercise training 6 days per week for 12 weeks. Exercise training consisted of either continuous, submaximal, endurance treadmill running (n = 10) or intermittent, high intensity, interval running (n = 10). Both modes of training enhanced the oxidation of palmityl-carnitine-malate in both mitochondrial populations (p < 0.05). However, the increase associated with the intermittent, high intensity exercise training was significantly greater than that achieved with the continuous exercise training (p < 0.05). Also, the increases associated with the IMF mitochondria were greater than the SS mitochondria (p < 0.05). These data suggest that high intensity, intermittent interval exercise training is more effective for stimulation of fatty acid oxidation than continuous submaximal exercise training and that this adaptation occurs preferentially within IMF mitochondria.Key words: muscle, subsarcolemmal mitochondria, intermyofibrillar mitochondria.

Effect of short-term fasting on the lipolytic response to theophylline

1991 ◽  
Vol 261 (4) ◽  
pp. E500-E504 ◽  
Author(s):  
E. J. Peters ◽  
S. Klein ◽  
R. R. Wolfe
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Indirect Calorimetry ◽  
Adenosine Receptors ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Acid Oxidation ◽  
Inhibitory Influence ◽  
Receptor Blockade ◽  
Short Term

We investigated the hypothesis that the increase in lipolysis that occurs in short-term (86-h) fasting is due to a decreased inhibitory influence of adenosine. In normal volunteers who fasted for 14 and 86 h, the response to adenosine receptor blockade was assessed by the infusion of theophylline at a rate sufficient to produce plasma concentrations (30 microM) that blocked adenosine receptors but that were well below the threshold for inhibition of phosphodiesterase. Lipolysis was assessed by determining the rate of appearance of glycerol using D-5-glycerol infusion. Fatty acid flux was also determined by means of [1-13C]palmitate infusion, and total fatty acid oxidation was determined by indirect calorimetry. There was a mild stimulatory effect of theophylline on lipolysis at 14 h. After the subjects fasted for 86 h, theophylline infusion caused a much greater increase in both lipolysis and fatty acid oxidation. These results suggest that the inhibitory effect of adenosine on lipolysis is increased during short-term fasting.

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.

scholarly journals Acetate Affects the Process of Lipid Metabolism in Rabbit Liver, Skeletal Muscle and Adipose Tissue

Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 799 ◽  
Author(s):  
Lei Liu ◽  
Chunyan Fu ◽  
Fuchang Li
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Synthesis ◽  
Lipid Accumulation ◽  
Acid Synthesis ◽  
Control Group ◽  
Acid Oxidation ◽  
Signal Pathways ◽  
Peroxisome Proliferator ◽  
Acid Uptake

Short-chain fatty acids (SCFAs) (a microbial fermentation production in the rabbit gut) have an important role in many physiological processes, which may be related to the reduced body fat of rabbits. In the present experiment, we study the function of acetate (a major SCFA in the rabbit gut) on fat metabolism. Ninety rabbits (40 days of age) were randomly divided into three groups: a sham control group (injection of saline for four days); a group experiencing subcutaneous injection of acetate for four days (2 g/kg BM per day, one injection each day, acetate); and a pair-fed sham treatment group. The results show that acetate-inhibited lipid accumulation by promoting lipolysis and fatty acid oxidation and inhibiting fatty acid synthesis. Activated G protein-coupled receptor 41/43, adenosine monophosphate activated protein kinase (AMPK) and extracellular-signal-regulated kinase (ERK) 1/2 signal pathways were likely to participate in the regulation in lipid accumulation of acetate. Acetate reduced hepatic triglyceride content by inhibiting fatty acid synthesis, enhancing fatty acid oxidation and lipid output. Inhibited peroxisome proliferator-activated receptor α (PPARα) and activated AMPK and ERK1/2 signal pathways were related to the process in liver. Acetate reduced intramuscular triglyceride level via increasing fatty acid uptake and fatty acid oxidation. PPARα was associated with the acetate-reduced intracellular fat content.

Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism

2005 ◽  
Vol 288 (5) ◽  
pp. C1074-C1082 ◽  
Author(s):  
Timothy R. Koves ◽  
Robert C. Noland ◽  
Andrew L. Bates ◽  
Sarah T. Henes ◽  
Deborah M. Muoio ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Exercise Training ◽  
Fatty Acid Oxidation ◽  
Treadmill Running ◽  
Hill Coefficient ◽  
Acid Oxidation ◽  
Oxidation Rates ◽  
Malonyl Coa ◽  
Mitochondrial Fatty Acid

Skeletal muscle contains two populations of mitochondria that appear to be differentially affected by disease and exercise training. It remains unclear how these mitochondrial subpopulations contribute to fiber type-related and/or training-induced changes in fatty acid oxidation and regulation of carnitine palmitoyltransferase-1β (CPT1β), the enzyme that controls mitochondrial fatty acid uptake in skeletal muscle. To this end, we found that fatty acid oxidation rates were 8.9-fold higher in subsarcolemmal mitochondria (SS) and 5.3-fold higher in intermyofibrillar mitochondria (IMF) that were isolated from red gastrocnemius (RG) compared with white gastrocnemius (WG) muscle, respectively. Malonyl-CoA (10 μM), a potent inhibitor of CPT1β, completely abolished fatty acid oxidation in SS and IMF mitochondria from WG, whereas oxidation rates in the corresponding fractions from RG were inhibited only 89% and 60%, respectively. Endurance training also elicited mitochondrial adaptations that resulted in enhanced fatty acid oxidation capacity. Ten weeks of treadmill running differentially increased palmitate oxidation rates 100% and 46% in SS and IMF mitochondria, respectively. In SS mitochondria, elevated fatty acid oxidation rates were accompanied by a 48% increase in citrate synthase activity but no change in CPT1 activity. Nonlinear regression analyses of mitochondrial fatty acid oxidation rates in the presence of 0–100 μM malonyl-CoA indicated that IC50 values were neither dependent on mitochondrial subpopulation nor affected by exercise training. However, in IMF mitochondria, training reduced the Hill coefficient ( P < 0.05), suggesting altered CPT1β kinetics. These results demonstrate that endurance exercise provokes subpopulation-specific changes in mitochondrial function that are characterized by enhanced fatty acid oxidation and modified CPT1β-malonyl-CoA dynamics.

scholarly journals Effect of Continuous Feeding of Ayu-Narezushi on Lipid Metabolism in a Mouse Model of Metabolic Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Takeshi Nishida ◽  
Koichi Tsuneyama ◽  
Yasuhiko Tago ◽  
Koji Nomura ◽  
Makoto Fujimoto ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Serum Triglyceride ◽  
Fermented Food ◽  
Control Group ◽  
Acid Oxidation ◽  
Mrna Levels ◽  
Mice Model ◽  
Continuous Feeding

Ayu-narezushi, a traditional Japanese fermented food, comprises abundant levels of lactic acid bacteria (LAB) and free amino acids. This study aimed to examine the potential beneficial effects of ayu-narezushi and investigated whether ayu-narezushi led to improvements in the Tsumura Suzuki obese diabetes (TSOD) mice model of spontaneous metabolic syndrome because useful LAB are known as probiotics that regulate intestinal function. In the present study, the increased body weight of the TSOD mice was attenuated in those fed the ayu-narezushi-comprised chow (ayu-narezushi group) compared with those fed the normal rodent chow (control group). Serum triglyceride and cholesterol levels were significantly lower in the Ayu-narezushi group than in the control group at 24 weeks of age. Furthermore, hepatic mRNA levels of carnitine-palmitoyl transferase 1 and acyl-CoA oxidase, which related to fatty acid oxidation, were significantly increased in the ayu-narezushi group than in the control group at 24 weeks of age. In conclusion, these results suggested that continuous feeding with ayu-narezushi improved obesity and dyslipidemia in the TSOD mice and that the activation of fatty acid oxidation in the liver might contribute to these improvements.

Poly-ion complex micelle effectively delivers CoA-conjugated CPT1A inhibitors to modulate lipid metabolism in brain cells

2021 ◽  
Author(s):  
West Kristian D. Paraiso ◽  
Jesús Garcia-Chica ◽  
Xavier Ariza ◽  
Sebastián Zagmutt ◽  
Shigeto Fukushima ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Oxidation ◽  
Carnitine Palmitoyltransferase ◽  
Brain Cells ◽  
Acid Oxidation ◽  
The Brain

Carnitine palmitoyltransferase 1A (CPT1A) is a central player in lipid metabolism, catalyzing the first committed step to fatty acid oxidation (FAO). Inhibiting CPT1A, especially in the brain, can have several...

scholarly journals Why does Brain Metabolism not Favor Burning of Fatty Acids to Provide Energy? - Reflections on Disadvantages of the Use of Free Fatty Acids as Fuel for Brain

2013 ◽  
Vol 33 (10) ◽  
pp. 1493-1499 ◽  
Author(s):  
Peter Schönfeld ◽  
Georg Reiser
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Brain Mitochondria ◽  
Neuronal Firing ◽  
Acid Oxidation ◽  
Nonesterified Fatty Acids ◽  
Atp Generation ◽  
Slow Passage ◽  
The Brain

It is puzzling that hydrogen-rich fatty acids are used only poorly as fuel in the brain. The long-standing belief that a slow passage of fatty acids across the blood–brain barrier might be the reason. However, this has been corrected by experimental results. Otherwise, accumulated nonesterified fatty acids or their activated derivatives could exert detrimental activities on mitochondria, which might trigger the mitochondrial route of apoptosis. Here, we draw attention to three particular problems: (1) ATP generation linked to β-oxidation of fatty acids demands more oxygen than glucose, thereby enhancing the risk for neurons to become hypoxic; (2) β-oxidation of fatty acids generates superoxide, which, taken together with the poor anti-oxidative defense in neurons, causes severe oxidative stress;(3) the rate of ATP generation based on adipose tissue-derived fatty acids is slower than that using blood glucose as fuel. Thus, in periods of extended continuous and rapid neuronal firing, fatty acid oxidation cannot guarantee rapid ATP generation in neurons. We conjecture that the disadvantages connected with using fatty acids as fuel have created evolutionary pressure on lowering the expression of the β-oxidation enzyme equipment in brain mitochondria to avoid extensive fatty acid oxidation and to favor glucose oxidation in brain.

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