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Your search keyword '"Lund, Jenny"' showing total 5 results
Start Over Author "Lund, Jenny" Topic lipid metabolism
5 results on '"Lund, Jenny"'

1. Treatment of human skeletal muscle cells with inhibitors of diacylglycerol acyltransferases 1 and 2 to explore isozyme-specific roles on lipid metabolism.

Author

Løvsletten NG, Vu H, Skagen C, Lund J, Kase ET, Thoresen GH, Zammit VA, and Rustan AC

Subjects
Acetic Acid metabolism, Glucose metabolism, Glycerol metabolism, Humans, Isoenzymes antagonists & inhibitors, Muscle Fibers, Skeletal drug effects, Muscle Fibers, Skeletal metabolism, Muscle, Skeletal metabolism, Oxidation-Reduction drug effects, Diacylglycerol O-Acyltransferase antagonists & inhibitors, Enzyme Inhibitors pharmacology, Lipid Metabolism drug effects, Muscle, Skeletal drug effects
Abstract

Diacylglycerol acyltransferases (DGAT) 1 and 2 catalyse the final step in triacylglycerol (TAG) synthesis, the esterification of fatty acyl-CoA to diacylglycerol. Despite catalysing the same reaction and being present in the same cell types, they exhibit different functions on lipid metabolism in various tissues. Yet, their roles in skeletal muscle remain poorly defined. In this study, we investigated how selective inhibitors of DGAT1 and DGAT2 affected lipid metabolism in human primary skeletal muscle cells. The results showed that DGAT1 was dominant in human skeletal muscle cells utilizing fatty acids (FAs) derived from various sources, both exogenously supplied FA, de novo synthesised FA, or FA derived from lipolysis, to generate TAG, as well as being involved in de novo synthesis of TAG. On the other hand, DGAT2 seemed to be specialised for de novo synthesis of TAG from glycerol-3-posphate only. Interestingly, DGAT activities were also important for regulating FA oxidation, indicating a key role in balancing FAs between storage in TAG and efficient utilization through oxidation. Finally, we observed that inhibition of DGAT enzymes could potentially alter glucose-FA interactions in skeletal muscle. In summary, treatment with DGAT1 or DGAT2 specific inhibitors resulted in different responses on lipid metabolism in human myotubes, indicating that the two enzymes play distinct roles in TAG metabolism in skeletal muscle.

Published
2020
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2. Higher lipid turnover and oxidation in cultured human myotubes from athletic versus sedentary young male subjects.

Author

Lund J, Helle SA, Li Y, Løvsletten NG, Stadheim HK, Jensen J, Kase ET, Thoresen GH, and Rustan AC

Subjects
Adult, Cells, Cultured, Humans, Male, Muscle Fibers, Skeletal cytology, Oxidation-Reduction, Oxygen Consumption, Athletes, Electron Transport Complex III metabolism, Lipid Metabolism, Mitochondria, Muscle metabolism, Muscle Fibers, Skeletal metabolism
Abstract

In this study we compared fatty acid (FA) metabolism in myotubes established from athletic and sedentary young subjects. Six healthy sedentary (maximal oxygen uptake (VO 2max ) ≤ 46 ml/kg/min) and six healthy athletic (VO 2max  > 60 ml/kg/min) young men were included. Myoblasts were cultured and differentiated to myotubes from satellite cells isolated from biopsy of musculus vastus lateralis. FA metabolism was studied in myotubes using [ 14 C]oleic acid. Lipid distribution was assessed by thin layer chromatography, and FA accumulation, lipolysis and re-esterification were measured by scintillation proximity assay. Gene and protein expressions were studied. Myotubes from athletic subjects showed lower FA accumulation, lower incorporation of FA into total lipids, triacylglycerol (TAG), diacylglycerol and cholesteryl ester, higher TAG-related lipolysis and re-esterification, and higher complete oxidation and incomplete β-oxidation of FA compared to myotubes from sedentary subjects. mRNA expression of the mitochondrial electron transport chain complex III gene UQCRB was higher in cells from athletic compared to sedentary. Myotubes established from athletic subjects have higher lipid turnover and oxidation compared to myotubes from sedentary subjects. Our findings suggest that cultured myotubes retain some of the phenotypic traits of their donors.

Published
2018
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3. Exercise in vivo marks human myotubes in vitro: Training-induced increase in lipid metabolism.

Author

Lund J, Rustan AC, Løvsletten NG, Mudry JM, Langleite TM, Feng YZ, Stensrud C, Brubak MG, Drevon CA, Birkeland KI, Kolnes KJ, Johansen EI, Tangen DS, Stadheim HK, Gulseth HL, Krook A, Kase ET, Jensen J, and Thoresen GH

Subjects
Adenylate Kinase genetics, Adenylate Kinase metabolism, Cells, Cultured, DNA Methylation, Epigenesis, Genetic, Fatty Acids metabolism, Glucose metabolism, Humans, Insulin physiology, Insulin Receptor Substrate Proteins genetics, Insulin Receptor Substrate Proteins metabolism, Male, Middle Aged, Mitochondria, Muscle metabolism, Mitochondrial Proteins metabolism, Phosphorylation, Protein Processing, Post-Translational, Resistance Training, Transcriptome, Lipid Metabolism, Muscle Fibers, Skeletal metabolism
Abstract

Background and Aims: Physical activity has preventive as well as therapeutic benefits for overweight subjects. In this study we aimed to examine effects of in vivo exercise on in vitro metabolic adaptations by studying energy metabolism in cultured myotubes isolated from biopsies taken before and after 12 weeks of extensive endurance and strength training, from healthy sedentary normal weight and overweight men., Methods: Healthy sedentary men, aged 40-62 years, with normal weight (body mass index (BMI) < 25 kg/m2) or overweight (BMI ≥ 25 kg/m2) were included. Fatty acid and glucose metabolism were studied in myotubes using [14C]oleic acid and [14C]glucose, respectively. Gene and protein expressions, as well as DNA methylation were measured for selected genes., Results: The 12-week training intervention improved endurance, strength and insulin sensitivity in vivo, and reduced the participants' body weight. Biopsy-derived cultured human myotubes after exercise showed increased total cellular oleic acid uptake (30%), oxidation (46%) and lipid accumulation (34%), as well as increased fractional glucose oxidation (14%) compared to cultures established prior to exercise. Most of these exercise-induced increases were significant in the overweight group, whereas the normal weight group showed no change in oleic acid or glucose metabolism., Conclusions: 12 weeks of combined endurance and strength training promoted increased lipid and glucose metabolism in biopsy-derived cultured human myotubes, showing that training in vivo are able to induce changes in human myotubes that are discernible in vitro.

Published
2017
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4. The molecular structure of thio-ether fatty acids influences PPAR-dependent regulation of lipid metabolism.

Author

Lund J, Stensrud C, Rajender, Bohov P, Thoresen GH, Berge RK, Wright M, Kamal A, Rustan AC, Miller AD, and Skorve J

Subjects
Dose-Response Relationship, Drug, Ethers chemical synthesis, Ethers chemistry, Fatty Acids chemical synthesis, Humans, Molecular Structure, Peroxisome Proliferator-Activated Receptors metabolism, Structure-Activity Relationship, Sulfhydryl Compounds chemical synthesis, Sulfhydryl Compounds chemistry, Ethers pharmacology, Fatty Acids chemistry, Fatty Acids pharmacology, Lipid Metabolism drug effects, Peroxisome Proliferator-Activated Receptors agonists, Sulfhydryl Compounds pharmacology
Abstract

Thio-ether fatty acids (THEFAs), including the parent 2-(tetradecylthio)acetic acid (TTA), are modified fatty acids (FAs) that have profound effects on lipid metabolism given that they are blocked for β-oxidation, and able to act as peroxisome proliferator-activated receptor (PPAR) agonists. Therefore, TTA in particular has been tested clinically for its therapeutic potential against metabolic syndrome related disorders. Here, we describe the preparation of THEFAs based on the TTA scaffold with either a double or a triple bond. These are tested in cultured human skeletal muscle cells (myotubes), either as free acid or following esterification as phospholipids, lysophospholipids or monoacylglycerols. Metabolic effects are assessed in terms of cellular bioavailabilities in myotubes, by FA substrate uptake and oxidation studies, and gene regulation studies with selected PPAR-regulated genes. We note that the inclusion of a triple bond promotes THEFA-mediated FA oxidation. Furthermore, esterification of THEFAs as lysophospholipids also promotes FA oxidation effects. Given that the apparent clinical benefits of TTA administration were offset by dose limitation and poor bioavailability, we discuss the possibility that a selection of our latest THEFAs and THEFA-containing lipids might be able to fulfill the therapeutic potential of the parent TTA while minimizing required doses for efficacy, side-effects and adverse reactions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Published
2016
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