Similar qualitative and quantitative changes of mitochondrial respiration following strength and endurance training in normoxia and hypoxia in sedentary humans

2011 ◽  
Vol 301 (4) ◽  
pp. R1078-R1087 ◽  
Author(s):  
Dominik Pesta ◽  
Florian Hoppel ◽  
Christian Macek ◽  
Hubert Messner ◽  
Martin Faulhaber ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Oxidative Phosphorylation ◽  
Strength Training ◽  
Endurance Training ◽  
Fatty Acid Oxidation ◽  
Muscle Mass ◽  
Mitochondrial Respiration ◽  
Vastus Lateralis ◽  
Acid Oxidation ◽  
Hypoxia Group

Endurance and strength training are established as distinct exercise modalities, increasing either mitochondrial density or myofibrillar units. Recent research, however, suggests that mitochondrial biogenesis is stimulated by both training modalities. To test the training “specificity” hypothesis, mitochondrial respiration was studied in permeabilized muscle fibers from 25 sedentary adults after endurance (ET) or strength training (ST) in normoxia or hypoxia [fraction of inspired oxygen (FiO2) = 21% or 13.5%]. Biopsies were taken from the musculus vastus lateralis, and cycle-ergometric incremental maximum oxygen uptake (V̇o2max) exercise tests were performed under normoxia, before and after the 10-wk training program. The main finding was a significant increase ( P < 0.05) of fatty acid oxidation capacity per muscle mass, after endurance and strength training under normoxia [2.6- and 2.4-fold for endurance training normoxia group (ETN) and strength training normoxia group (STN); n = 8 and 3] and hypoxia [2.0-fold for the endurance training hypoxia group (ETH) and strength training hypoxia group (STH); n = 7 and 7], and higher coupling control of oxidative phosphorylation. The enhanced lipid oxidative phosphorylation (OXPHOS) capacity was mainly (87%) due to qualitative mitochondrial changes increasing the relative capacity for fatty acid oxidation ( P < 0.01). Mitochondrial tissue-density contributed to a smaller extent (13%), reflected by the gain in muscle mass-specific respiratory capacity with a physiological substrate cocktail (glutamate, malate, succinate, and octanoylcarnitine). No significant increase was observed in mitochondrial DNA (mtDNA) content. Physiological OXPHOS capacity increased significantly in ETN ( P < 0.01), with the same trend in ETH and STH ( P < 0.1). The limitation of flux by the phosphorylation system was diminished after training. Importantly, key mitochondrial adaptations were similar after endurance and strength training, regardless of normoxic or hypoxic exercise. The transition from a sedentary to an active lifestyle induced muscular changes of mitochondrial quality representative of mitochondrial health.

scholarly journals High Incomplete Skeletal Muscle Fatty Acid Oxidation Explains Low Muscle Insulin Sensitivity in Poorly Controlled T2D

2017 ◽  
Vol 103 (3) ◽  
pp. 882-889 ◽  
Author(s):  
Timothy P Gavin ◽  
Jacob M Ernst ◽  
Hyo-Bum Kwak ◽  
Sarah E Caudill ◽  
Melissa A Reed ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Oxidation ◽  
Mitochondrial Respiration ◽  
Vastus Lateralis ◽  
Acid Oxidation ◽  
Vastus Lateralis Muscle ◽  
Intravenous Glucose ◽  
Mitochondrial Respiratory

Abstract Context Almost 50% of type 2 diabetic (T2D) patients are poorly controlled [glycated hemoglobin (HbA1c) ≥ 7%]; however, the mechanisms responsible for progressively worsening glycemic control are poorly understood. Lower skeletal muscle mitochondrial respiratory capacity is associated with low insulin sensitivity and the development of T2D. Objective We investigated if skeletal muscle insulin sensitivity (SI) was different between well-controlled T2D (WCD) and poorly controlled T2D (PCD) and if the difference was associated with differences resulting from mitochondrial respiratory function. Design Vastus lateralis muscle mitochondrial respiration, mitochondrial content, mitochondrial enzyme activity, and fatty acid oxidation (FAO) were measured. SI and the acute response to glucose (AIRg) were calculated by MINMOD analysis from glucose and insulin obtained during a modified, frequently sampled, intravenous glucose tolerance test. Results SI and AIRg were lower in PCD than WCD. Muscle incomplete FAO was greater in PCD than WCD and greater incomplete FAO was associated with lower SI and higher HbA1c. Hydroxyacyl-coenzyme A dehydrogenase expression and activity were greater in PCD than WCD. There was no difference in maximal mitochondrial respiration or content between WCD and PCD. Conclusion The current results suggest that greater skeletal muscle incomplete FAO in poorly controlled T2D is due to elevated β oxidation and is associated with worsening muscle SI.

scholarly journals Progesterone receptor membrane component 1 reduces cardiac steatosis and lipotoxicity via activation of fatty acid oxidation and mitochondrial respiration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sang R. Lee ◽  
Jun H. Heo ◽  
Seong Lae Jo ◽  
Globinna Kim ◽  
Su Jung Kim ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Progesterone Receptor ◽  
Fatty Acid Oxidation ◽  
Mitochondrial Respiration ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Membrane Component ◽  
Markers Of Inflammation ◽  
Receptor Membrane

AbstractObesity is implicated in cardiovascular disease and heart failure. When fatty acids are transported to and not adequately oxidized in cardiac cells, they accumulate, causing lipotoxicity in the heart. Since hepatic progesterone receptor membrane component 1 (Pgrmc1) suppressed de novo lipogenesis in a previous study, it was questioned whether cardiac Pgrmc1 protects against lipotoxicity. Hence, we focused on the role of cardiac Pgrmc1 in basal (Resting), glucose-dominant (Refed) and lipid-dominant high-fat diet (HFD) conditions. Pgrmc1 KO mice showed high FFA levels and low glucose levels compared to wild-type (WT) mice. Pgrmc1 KO mice presented low number of mitochondrial DNA copies in heart, and it was concomitantly observed with low expression of TCA cycle genes and oxidative phosphorylation genes. Pgrmc1 absence in heart presented low fatty acid oxidation activity in all conditions, but the production of acetyl-CoA and ATP was in pronounced suppression only in HFD condition. Furthermore, HFD Pgrmc1 KO mice resulted in high cardiac fatty acyl-CoA levels and TG level. Accordingly, HFD Pgrmc1 KO mice were prone to cardiac lipotoxicity, featuring high levels in markers of inflammation, endoplasmic reticulum stress, oxidative stress, fibrosis, and heart failure. In vitro study, it was also confirmed that Pgrmc1 enhances rates of mitochondrial respiration and fatty acid oxidation. This study is clinically important because mitochondrial defects in Pgrmc1 KO mice hearts represent the late phase of cardiac failure.

scholarly journals miR-21-5p regulates mitochondrial respiration and lipid content in H9C2 cells

2019 ◽  
Vol 316 (3) ◽  
pp. H710-H721 ◽  
Author(s):  
Victoria L. Nasci ◽  
Sandra Chuppa ◽  
Lindsey Griswold ◽  
Kathryn A. Goodreau ◽  
Ranjan K. Dash ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Content ◽  
Mitochondrial Respiration ◽  
Acid Oxidation ◽  
H9c2 Cells ◽  
Cellular Lipid ◽  
Transfected Cells

Cardiovascular-related pathologies are the single leading cause of death in patients with chronic kidney disease (CKD). Previously, we found that a 5/6th nephrectomy model of CKD leads to an upregulation of miR-21-5p in the left ventricle, targeting peroxisome proliferator-activated receptor-α and altering the expression of numerous transcripts involved with fatty acid oxidation and glycolysis. In the present study, we evaluated the potential for knockdown or overexpression of miR-21-5p to regulate lipid content, lipid peroxidation, and mitochondrial respiration in H9C2 cells. Cells were transfected with anti-miR-21-5p (40 nM), pre-miR-21-5p (20 nM), or the appropriate scrambled oligonucleotide controls before lipid treatment in culture or as part of the Agilent Seahorse XF fatty acid oxidation assay. Overexpression of miR-21-5p attenuated the lipid-induced increase in cellular lipid content, whereas suppression of miR-21-5p augmented it. The abundance of malondialdehyde, a product of lipid peroxidation, was significantly increased with lipid treatment in control cells but attenuated in pre-miR-21-5p-transfected cells. This suggests that miR-21-5p reduces oxidative stress. The cellular oxygen consumption rate (OCR) was increased in both pre-miR-21-5p- and anti-miR-21-5p-transfected cells. Levels of intracellular ATP were significantly higher in anti-mR-21-5p-transfected cells. Pre-miR-21-5p blocked additional increases in OCR in response to etomoxir and palmitic acid. Conversely, anti-miR-21-5p-transfected cells exhibited reduced OCR with both etomoxir and palmitic acid, and the glycolytic capacity was concomitantly reduced. Together, these results indicate that overexpression of miR-21-5p attenuates both lipid content and lipid peroxidation in H9C2 cells. This likely occurs by reducing cellular lipid uptake and utilization, shifting cellular metabolism toward reliance on the glycolytic pathway. NEW & NOTEWORTHY Both overexpression and suppression of miR-21-5p augment basal and maximal mitochondrial respiration. Our data suggest that reliance on glycolytic and fatty acid oxidation pathways can be modulated by the abundance of miR-21-5p within the cell. miR-21-5p regulation of mitochondrial respiration can be modulated by extracellular lipids.

Fatty acid kinetic responses to running above or below lactate threshold

1995 ◽  
Vol 79 (2) ◽  
pp. 439-447 ◽  
Author(s):  
J. A. Kanaley ◽  
C. D. Mottram ◽  
P. D. Scanlon ◽  
M. D. Jensen
Keyword(s):  
Fatty Acid ◽  
Endurance Training ◽  
Fatty Acid Oxidation ◽  
Indirect Calorimetry ◽  
Lactate Threshold ◽  
Exercise Group ◽  
Acid Oxidation ◽  
Running Exercise ◽  
Marathon Training ◽  
Energy Demands

During running exercise above the lactate threshold (LT), it is unknown whether free fatty acid (FFA) mobilization can meet the energy demands for fatty acid oxidation. This study was performed to determine whether FFA availability is reduced during running exercise above compared with below the LT and to assess whether the level of endurance training influences FFA mobilization. Twelve marathon runners and 12 moderately trained runners ran at a workload that was either above or below their individual LT. Fatty acid oxidation (indirect calorimetry) and FFA release ([1–14C]palmitate) were measured at baseline, throughout exercise, and at recovery. The plasma FFA rate of appearance increased during exercise in both groups; running above or below the LT, but the total FFA availability for 30 min of exercise was greater (P < 0.01) in the below LT group (marathon, 23 +/- 2 mmol; moderate, 21 +/- 2 mmol) than in the above LT group (18 +/- 3 and 13 +/- 3 mmol, respectively). Total fatty acid oxidation (indirect calorimetry) greatly exceeded circulating FFA availability, regardless of training or exercise group (P < 0.01). No statistically significant exercise intensity or training differences in fatty acid oxidation were found (above LT: marathon, 71 +/- 12, moderate, 64 +/- 17 mmol/30 min; below LT: marathon 91 +/- 12, moderate, 60 +/- 5 mmol/30 min). In conclusion, during exercise above or below LT, circulating FFA cannot meet the oxidative needs and intramuscular triglyceride stores must be utilized. Further marathon training does not enhance effective adipose tissue lipolysis during exercise compared with moderate endurance training.

65 Fatty acid oxidation in human skeletal muscle mitochondria determined by oxidative phosphorylation as a function of age

Mitochondrion ◽  
2007 ◽  
Vol 7 (6) ◽  
pp. 422-423
Author(s):  
George Kypriotakis ◽  
Bruce H. Cohen ◽  
Sumit Parikh ◽  
Douglas S. Kerr ◽  
Charles L. Hoppel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Oxidative Phosphorylation ◽  
Fatty Acid Oxidation ◽  
Human Skeletal Muscle ◽  
Acid Oxidation ◽  
Muscle Mitochondria ◽  
Skeletal Muscle Mitochondria

scholarly journals MON-672 Progesterone Receptor Membrane Component 1 Suppresses Lipid Accumulation and Lipotoxicity in Animal Model of Diabetic Cardiomyopathy (DCM)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sang R Lee ◽  
Eui-ju Hong
Keyword(s):  
Fatty Acid ◽  
Progesterone Receptor ◽  
Fatty Acid Oxidation ◽  
Diabetic Cardiomyopathy ◽  
Mitochondrial Respiration ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Membrane Component

Abstract Diabetic cardiomyopathy (DCM) is one of the complications triggered by type II diabetes (T2D) (1). When free fatty acids (FFA) are abundant in insulin resistant pre-diabetic patients because of adipose lipolysis, FFA tends to move toward heart (2). Lipid accumulation can cause cardiac lipotoxicity and exacerbate DCM (3). In previous study, Pgrmc1 has been identified to associate with fatty acid synthesis (4). Therefore, we assumed that Pgrmc1 will associate with DCM. By feeding high-fat diet for 8 weeks and injecting streptozotocin (30mg/kg), T2D and DCM were induced. The lipid accumulation was exacerbated in T2D-induced Pgrmc1 KO heart, and FFA level was also high. Levels of lipid metabolic genes showed the tendency for lipid accumulation and lipotoxicity, and glycolysis was induced in T2D-induced Pgrmc1 KO heart. Though glycolysis presents higher efficiency for energy production in cardiomyopathy (5), it did not compensate the impairment of mitochondrial respiration in Pgrmc1 KO heart. High-fat diet and streptozotocin could not be the interfering factors, because suppression of fatty acid oxidation, induction of glycolysis, and impairment of mitochondrial respiration were observed similarly in post-prandial mice which were fed with normal chow. Insulin was excluded for interfering factor as cell line with serum starvation showed mitochondrial suppression and glycolytic induction in flux analyzer analysis in Pgrmc1 knockdown. Conversely, induction of fatty acid oxidation and suppression of glycolysis were observed in 72 h fasting of Pgrmc1 KO heart, suggesting the nutrition is closely associated with the metabolic modulation of Pgrmc1 on heart. This metabolic phenotype of Pgrmc1 KO heart consequently exacerbated DCM by showing high levels of fibrosis, inflammation, endoplasmic reticulum stress, and oxidative stress. References: (1) Jia G, Hill MA, Sowers JR. Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity. Circulation research. 2018;122:624-38. (2) Noll C, Carpentier AC. Dietary fatty acid metabolism in prediabetes. Current opinion in lipidology. 2017;28:1-10. (3) Goldberg IJ, Trent CM, Schulze PC. Lipid metabolism and toxicity in the heart. Cell metabolism. 2012;15:805-12. (4) Lee SR, Kwon SW, Kaya P, Lee YH, Lee JG, Kim G, et al. Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis. Scientific reports. 2018;8:15711. (5) Nagoshi T, Yoshimura M, Rosano GM, Lopaschuk GD, Mochizuki S. Optimization of cardiac metabolism in heart failure. Current pharmaceutical design. 2011;17:3846-53.

Human skeletal muscle malonyl-CoA at rest and during prolonged submaximal exercise

1996 ◽  
Vol 270 (3) ◽  
pp. E541-E544 ◽  
Author(s):  
L. M. Odland ◽  
G. J. Heigenhauser ◽  
G. D. Lopaschuk ◽  
L. L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
High Performance ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Submaximal Exercise ◽  
Acid Oxidation ◽  
Vastus Lateralis Muscle ◽  
Malonyl Coa

Previous literature has indicated that contraction-induced decreases in malonyl-CoA are instrumental in the regulation of fatty acid oxidation during prolonged submaximal exercise. This study was designed to measure malonyl-CoA in human vastus lateralis muscle at rest and during submaximal exercise. Eight males and one female cycled for 70 min (10 min at 40% and 60 min at 65% maximal O2 uptake). Needle biopsies were obtained at rest and at 10 min, 20 min, and 70 min of exercise. Malonyl-CoA content in preexercise biopsy samples determined by high-performance liquid chromatography (HPLC) was 1.53 +/- 0.18 micromol/kg dry mass (dm). Malonyl-CoA content did not change significantly during exercise (1.39 +/- 0.21 at 10 min, 1.46 +/- 0.14 at 20 min, and 1.22 +/- 0.15 micromol/kg dm at 70 min). In contrast, malonyl-CoA content determined by HPLC in perfused rat red gastrocnemius muscle decreased significantly during 20 min of stimulation at 0.7 Hz [3.44 +/- 0.54 to 1.64 +/- 0.23 nmol/g dm, (n=9)]. We conclude that human skeletal muscle malonyl-CoA content 1) is less than reported in rat skeletal muscle at rest, 2) does not decrease with prolonged submaximal exercise, and 3) is not predictive of increased fatty acid oxidation during exercise.

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