Fatty Acid Oxidation in Mitochondria from Needle Biopsy Samples of Human Skeletal Muscle

1984 ◽  
Vol 66 (2) ◽  
pp. 173-178 ◽  
Author(s):  
K. Gohil ◽  
D. A. Jones ◽  
R. H. T. Edwards
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome C ◽  
Needle Biopsy ◽  
Human Skeletal Muscle ◽  
Normal Subjects ◽  
Normal Activity ◽  
Carnitine Palmitoyltransferase ◽  
Acid Oxidation ◽  
Palmitoyl Carnitine ◽  
Mitochondrial Abnormality

1. Activities for the oxidation of palmitoyl-carnitine, of palmitoyl-CoA and of carnitine palmitoyltransferase were measured in mitochondria prepared from needle biopsy samples of human skeletal muscle. Results are presented for nine normal subjects and 18 patients in whom there was evidence of mitochondrial abnormality. 2. Palmitoylcarnitine and palmitoyl-CoA oxidation were measured spectrophotometrically by following the reduction of added cytochrome c in the presence of cyanide. 3. Because of large variations in the activities between subjects it was essential to express the three activities per unit of cytochrome c oxidase activity to demonstrate unambiguous specific alterations in the activities. 4. In most of the patients the order of the three activities was similar to that in the normal subjects. However, in five cases the activity for palmitoylcarnitine oxidation was less than 4% of the mean normal value. In two of these patients, the low activity could be accounted for by very low (<10% normal) activity of carnitine palmitoyltransferase (CPT). In another two patients the activity of CPT was normal but that of palmitoyl-CoA dehydrogenase (a measure of β-oxidation) was very low.

scholarly journals Lipid oxidation is reduced in obese human skeletal muscle

2000 ◽  
Vol 279 (5) ◽  
pp. E1039-E1044 ◽  
Author(s):  
Jong-Yeon Kim ◽  
Robert C. Hickner ◽  
Ronald L. Cortright ◽  
G. Lynis Dohm ◽  
Joseph A. Houmard
Keyword(s):  
Skeletal Muscle ◽  
Lipid Oxidation ◽  
Human Skeletal Muscle ◽  
Citrate Synthase ◽  
Acid Oxidation ◽  
Cellular Mechanisms ◽  
Mitochondrial Content ◽  
Palmitoyl Carnitine ◽  
Obese Human ◽  
Carnitine Palmitoyltransferase 1

The purpose of this study was to discern cellular mechanisms that contribute to the suppression of lipid oxidation in the skeletal muscle of obese individuals. Muscle was obtained from obese [body mass index (BMI), 38.3 ± 3.1 kg/m2] and lean (BMI, 23.8 ± 0.9 kg/m2) women, and fatty acid oxidation was studied by measuring 14CO2 production from14C-labeled fatty acids. Palmitate oxidation, which is at least partially dependent on carnitine palmitoyltransferase-1 (CPT-1) activity, was depressed ( P < 0.05) by ≈50% with obesity (6.8 ± 2.2 vs. 13.7 ± 1.4 nmole CO2 · g−1 · h−1). The CPT-1-independent event of palmitoyl carnitine oxidation was also depressed ( P < 0.01) by ≈45%. There were significant negative relationships ( P < 0.05) for adiposity with palmitate ( r = −0.76) and palmitoyl carnitine ( r = −0.82) oxidation. Muscle CPT-1 and citrate synthase activity, an index of mitochondrial content, were also significantly ( P < 0.05) reduced (≈35%) with obesity. CPT-1 ( r = −0.48) and citrate synthase ( r = −0.65) activities were significantly ( P < 0.05) related to adiposity. These data suggest that lesions at CPT-1 and post-CPT-1 events, such as mitochondrial content, contribute to the reduced reliance on fat oxidation evident in human skeletal muscle with obesity.

scholarly journals Overexpression of Long-Chain Acyl-CoA Synthetase 5 Increases Fatty Acid Oxidation and Free Radical Formation While Attenuating Insulin Signaling in Primary Human Skeletal Myotubes

2019 ◽  
Vol 16 (7) ◽  
pp. 1157 ◽  
Author(s):  
Hyo-Bum Kwak ◽  
Tracey Woodlief ◽  
Thomas Green ◽  
Julie Cox ◽  
Robert Hickner ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Free Radical ◽  
Fatty Acid Oxidation ◽  
Insulin Signaling ◽  
Human Skeletal Muscle ◽  
Acid Oxidation ◽  
Protein Levels ◽  
Human Skeletal Muscle Cells ◽  
Mitochondrial Fatty Acid

In rodent skeletal muscle, acyl-coenzyme A (CoA) synthetase 5 (ACSL-5) is suggested to localize to the mitochondria but its precise function in human skeletal muscle is unknown. The purpose of these studies was to define the role of ACSL-5 in mitochondrial fatty acid metabolism and the potential effects on insulin action in human skeletal muscle cells (HSKMC). Primary myoblasts isolated from vastus lateralis (obese women (body mass index (BMI) = 34.7 ± 3.1 kg/m2)) were transfected with ACSL-5 plasmid DNA or green fluorescent protein (GFP) vector (control), differentiated into myotubes, and harvested (7 days). HSKMC were assayed for complete and incomplete fatty acid oxidation ([1-14C] palmitate) or permeabilized to determine mitochondrial respiratory capacity (basal (non-ADP stimulated state 4), maximal uncoupled (carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP)-linked) respiration, and free radical (superoxide) emitting potential). Protein levels of ACSL-5 were 2-fold higher in ACSL-5 overexpressed HSKMC. Both complete and incomplete fatty acid oxidation increased by 2-fold (p < 0.05). In permeabilized HSKMC, ACSL-5 overexpression significantly increased basal and maximal uncoupled respiration (p < 0.05). Unexpectedly, however, elevated ACSL-5 expression increased mitochondrial superoxide production (+30%), which was associated with a significant reduction (p < 0.05) in insulin-stimulated p-Akt and p-AS160 protein levels. We concluded that ACSL-5 in human skeletal muscle functions to increase mitochondrial fatty acid oxidation, but contrary to conventional wisdom, is associated with increased free radical production and reduced insulin signaling.

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 A case of carnitine palmitoyltransferase II deficiency in human skeletal muscle

FEBS Letters ◽  
1988 ◽  
Vol 241 (1-2) ◽  
pp. 126-130 ◽  
Author(s):  
Rajinder Singh ◽  
Isobel.M. Shepherd ◽  
Jerry P. Derrick ◽  
Rona R. Ramsay ◽  
H.Stanley A. Sherratt ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Carnitine Palmitoyltransferase ◽  
Carnitine Palmitoyltransferase Ii

scholarly journals Chlorpromazine and carnitine-dependency of rat liver peroxisomal β-oxidation of long-chain fatty acids

1987 ◽  
Vol 241 (3) ◽  
pp. 783-791 ◽  
Author(s):  
J Vamecq
Keyword(s):  
Fatty Acids ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Rat Liver ◽  
Fatty Acyl ◽  
Carnitine Palmitoyltransferase ◽  
Acid Oxidation ◽  
Synthetase Activity ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid

The enzyme targets for chlorpromazine inhibition of rat liver peroxisomal and mitochondrial oxidations of fatty acids were studied. Effects of chlorpromazine on total fatty acyl-CoA synthetase activity, on both the first and the third steps of peroxisomal beta-oxidation, on the entry of fatty acyl-CoA esters into the peroxisome and on catalase activity, which allows breakdown of the H2O2 generated during the acyl-CoA oxidase step, were analysed. On all these metabolic processes, chlorpromazine was found to have no inhibitory action. Conversely, peroxisomal carnitine octanoyltransferase activity was depressed by 0.2-1 mM-chlorpromazine, which also inhibits mitochondrial carnitine palmitoyltransferase activity in all conditions in which these enzyme reactions are assayed. Different patterns of inhibition by the drug were, however, demonstrated for both these enzyme activities. Inhibitory effects of chlorpromazine on mitochondrial cytochrome c oxidase activity were also described. Inhibitions of both cytochrome c oxidase and carnitine palmitoyltransferase are proposed to explain the decreased mitochondrial fatty acid oxidation with 0.4-1.0 mM-chlorpromazine reported by Leighton, Persico & Necochea [(1984) Biochem. Biophys. Res. Commun. 120, 505-511], whereas depression by the drug of carnitine octanoyltransferase activity is presented as the factor responsible for the decreased peroxisomal beta-oxidizing activity described by the above workers.

scholarly journals Differential epigenetic and transcriptional response of the skeletal muscle carnitine palmitoyltransferase 1B (CPT1B) gene to lipid exposure with obesity

2015 ◽  
Vol 309 (4) ◽  
pp. E345-E356 ◽  
Author(s):  
Jill M. Maples ◽  
Jeffrey J. Brault ◽  
Carol A. Witczak ◽  
Sanghee Park ◽  
Monica J. Hubal ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Transcription Factor ◽  
Fatty Acid ◽  
Histone Acetylation ◽  
Human Skeletal Muscle ◽  
Epigenetic Modifications ◽  
Carnitine Palmitoyltransferase ◽  
Severely Obese ◽  
Metabolic Inflexibility

The ability to increase fatty acid oxidation (FAO) in response to dietary lipid is impaired in the skeletal muscle of obese individuals, which is associated with a failure to coordinately upregulate genes involved with FAO. While the molecular mechanisms contributing to this metabolic inflexibility are not evident, a possible candidate is carnitine palmitoyltransferase-1B (CPT1B), which is a rate-limiting step in FAO. The present study was undertaken to determine if the differential response of skeletal muscle CPT1B gene transcription to lipid between lean and severely obese subjects is linked to epigenetic modifications (DNA methylation and histone acetylation) that impact transcriptional activation. In primary human skeletal muscle cultures the expression of CPT1B was blunted in severely obese women compared with their lean counterparts in response to lipid, which was accompanied by changes in CpG methylation, H3/H4 histone acetylation, and peroxisome proliferator-activated receptor-δ and hepatocyte nuclear factor 4α transcription factor occupancy at the CPT1B promoter. Methylation of specific CpG sites in the CPT1B promoter that correlated with CPT1B transcript level blocked the binding of the transcription factor upstream stimulatory factor, suggesting a potential causal mechanism. These findings indicate that epigenetic modifications may play important roles in the regulation of CPT1B in response to a physiologically relevant lipid mixture in human skeletal muscle, a major site of fatty acid catabolism, and that differential DNA methylation may underlie the depressed expression of CPT1B in response to lipid, contributing to the metabolic inflexibility associated with severe obesity.

scholarly journals Flux Control of Cytochrome c Oxidase in Human Skeletal Muscle

2000 ◽  
Vol 275 (36) ◽  
pp. 27741-27745 ◽  
Author(s):  
Wolfram S. Kunz ◽  
Alexei Kudin ◽  
Stefan Vielhaber ◽  
Christian E. Elger ◽  
Giuseppe Attardi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Human Skeletal Muscle ◽  
Flux Control

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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