Eili Tranheim Kase

• Dalmao-Fernandez, Andrea; Katare, Parmeshwar Bajirao; Bakke, Hege Gilbø; Hamarsland, Håvard; Ellefsen, Stian & Singh, Sachin [Vis alle 10 forfattere av denne artikkelen] (2025). The use of three-dimensional primary human myospheres to explore skeletal muscle effects of in vivo krill oil supplementation. In vitro models. ISSN 2731-3433. 4(2), s. 145–155. doi: 10.1007/s44164-025-00087-6. Fulltekst i vitenarkiv Vis sammendrag

  Supplementation with krill oil has shown effects on whole-body lipid and glucose metabolism, as well as on skeletal muscle strength and function. We previously showed that krill oil intervention in vivo promoted fatty acid metabolism and protein synthesis in cultured human myotubes in a two-dimensional (2D) model. The aim of this study was to explore the effects of krill oil supplementation in vivo in a 3D myosphere model, and to compare a the human skeletal muscle 3D cell model to a 2D model. Myospheres were formed from myoblasts obtained before and after 7 weeks of in vivo krill oil intervention. Glucose and oleic acid metabolism were assessed, and transcriptomic and proteomic analyses were performed. In vivo intervention with krill oil increased glucose metabolism in myospheres, while no effect was observed on fatty acid metabolism. Transcriptomic analyses of myospheres after krill oil intervention showed increased expression of genes involved in pathways like motor proteins and hypertrophy, as well as in calcium signaling, of which motor proteins and hypertrophy pathways have not been described in 2D myotube cultures. Proteomic analyses after krill oil intervention showed increased expression of proteins in glycolysis/gluconeogenesis and fatty acid degradation. Comparison of proteins expressed in the 3D myosphere model and the 2D myotube model at the basal level showed that in myospheres, mitochondrial gene expression and translation dominated, while in 2D cultures, mitochondrial organization and response to oxidative stress were more important. These findings suggest that in vivo krill oil intervention induces different metabolic effects when comparing 3D and 2D cultures. In contrast to the 2D model, data obtained with the 3D model showed gene expression changes that are more compatible with previously observed results in vivo concerning skeletal muscle motoric function. Hence, the 3D cell model might better reflect krill oil-induced modifications in skeletal muscle performance in vivo than the 2D model.

• Skagen, Christine; Stevanovic, Stanislava; Bakke, Hege Gilbø; Nyman, Tuula Anneli; Stensland, Maria & Kase, Eili Tranheim [Vis alle 9 forfattere av denne artikkelen] (2025). Reduced lipid and glucose oxidation and reduced lipid synthesis in AMPKα2/ myotubes. Archives of Physiology and Biochemistry. ISSN 1381-3455. 131(3), s. 483–492. doi: 10.1080/13813455.2024.2449409. Fulltekst i vitenarkiv Vis sammendrag

  Adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in regulation ofmetabolic homeostasis. To understand the role of the catalytic α2 subunit of AMPK in skeletal muscleenergy metabolism, myotube cultures were established from AMPKα2+/+ and AMPKα2-/- mice. Myotubesfrom AMPKα2-/- mice had lower basal oleic acid and glucose oxidation compared to myotubes fromAMPKα2+/+ mice. However, the relative response to mitochondrial uncoupling was increased for oleicacid oxidation. Incorporation of acetate into lipids was also lower in myotubes from AMPKα2-/- mice.Proteomics analysis revealed that AMPKα2-/- myotubes had upregulated pathways related to mitochondrialfunction and fatty acid oxidation, and decreased pathways related to fatty acid biosynthesis. Inconclusion, ablation of AMPKα2 catalytic subunit in skeletal muscle cells resulted in reduced basaloxidation of glucose and fatty acids, however upregulated pathways related to mitochondrial functionand fatty acid oxidation and reduced lipid formation

• Katare, Parmeshwar Bajirao; Dalmao-Fernandez, Andrea; Mengeste, Abel Mulu; Navabakbar, Farnaz; Hamarsland, Håvard & Ellefsen, Stian [Vis alle 12 forfattere av denne artikkelen] (2024). Krill oil supplementation in vivo promotes increased fuel metabolism and protein synthesis in cultured human skeletal muscle cells. Frontiers in Nutrition. 11:1452768, s. 1–14. doi: 10.3389/fnut.2024.1452768. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Krill oil is a dietary supplement derived from Antarctic krill; a small crustacean found in the ocean. Krill oil is a rich source of omega-3 fatty acids, specifically eicosapentaenoic acid and docosahexaenoic acid, as well as the antioxidant astaxanthin. The aim of this study was to investigate the effects of krill oil supplementation, compared to placebo oil (high oleic sunflower oil added astaxanthin), in vivo on energy metabolism and substrate turnover in human skeletal muscle cells. Methods: Skeletal muscle cells (myotubes) were obtained before and after a 7-week krill oil or placebo oil intervention, and glucose and oleic acid metabolism and leucine accumulation, as well as effects of different stimuli in vitro, were studied in the myotubes. The functional data were combined with proteomic and transcriptomic analyses. Results: In vivo intervention with krill oil increased oleic acid oxidation and leucine accumulation in skeletal muscle cells, however no effects were observed on glucose metabolism. The krill oil-intervention-induced increase in oleic acid oxidation correlated negatively with changes in serum low-density lipoprotein (LDL) concentration. In addition, myotubes were also exposed to krill oil in vitro. The in vitro study revealed that 24 h of krill oil treatment increased both glucose and oleic acid metabolism in myotubes, enhancing energy substrate utilization. Transcriptomic analysis comparing myotubes obtained before and after krill oil supplementation identified differentially expressed genes associated with e.g., glycolysis/gluconeogenesis, metabolic pathways and calcium signaling pathway, while proteomic analysis demonstrated upregulation of e.g., LDL-receptor in myotubes obtained after the krill oil intervention. Conclusion: These findings suggest that krill oil intervention promotes increased fuel metabolism and protein synthesis in human skeletal muscle cells, with potential implications for metabolic health.

• Stevanovic, Stanislava; Dalmao-Fernandez, Andrea; Mohamed, Derya; Nyman, Tuula Anneli; Kostovski, Emil & Iversen, Per Ole [Vis alle 11 forfattere av denne artikkelen] (2024). Time-dependent reduction in oxidative capacity among cultured myotubes from spinal cord injured individuals. Acta Physiologica. ISSN 1748-1708. 240:e14156(7), s. 1–15. doi: 10.1111/apha.14156. Fulltekst i vitenarkiv Vis sammendrag

  Background Skeletal muscle adapts in reaction to contractile activity to efficiently utilize energy substrates, primarily glucose and free fatty acids (FA). Inactivity leads to atrophy and a change in energy utilization in individuals with spinal cord injury (SCI). The present study aimed to characterize possible inactivity-related differences in the energy metabolism between skeletal muscle cells cultured from satellite cells isolated 1- and 12-months post-SCI. Methods To characterize inactivity-related disturbances in spinal cord injury, we studied skeletal muscle cells isolated from SCI subjects. Cell cultures were established from biopsy samples from musculus vastus lateralis from subjects with SCI 1 and 12 months after the injury. The myoblasts were proliferated and differentiated into myotubes before fatty acid and glucose metabolism were assessed and gene and protein expressions were measured. Results The results showed that glucose uptake was increased, while oleic acid oxidation was reduced at 12 months compared to 1 month. mRNA expressions of PPARGC1α, the master regulator of mitochondrial biogenesis, and MYH2, a determinant of muscle fiber type, were significantly reduced at 12 months. Proteomic analysis showed reduced expression of several mitochondrial proteins. Conclusion In conclusion, skeletal muscle cells isolated from immobilized subjects 12 months compared to 1 month after SCI showed reduced fatty acid metabolism and reduced expression of mitochondrial proteins, indicating an increased loss of oxidative capacity with time after injury.

• Krapf, Solveig; Lund, Jenny; Bakke, Hege Gilbø; Nyman, Tuula Anneli; Bartesaghi, Stefano & Peng, Xiao-Rong [Vis alle 9 forfattere av denne artikkelen] (2023). SENP2 knockdown in human adipocytes reduces glucose metabolism and lipid accumulation, while increases lipid oxidation. Metabolism Open. 18. doi: 10.1016/j.metop.2023.100234. Fulltekst i vitenarkiv Vis sammendrag

  Adipose tissue is one of the main regulative sites for energy metabolism. Excess lipid storage and expansion of white adipose tissue (WAT) is the primary contributor to obesity, a strong predisposing factor for development of insulin resistance. Sentrin-specific protease (SENP) 2 has been shown to play a role in metabolism in murine fat and skeletal muscle cells, and we have previously demonstrated its role in energy metabolism of human skeletal muscle cells. In the present work, we have investigated the impact of SENP2 on fatty acid and glucose metabolism in primary human fat cells by using cultured primary human adipocytes to knock down the SENP2 gene. Glucose uptake and oxidation, as well as accumulation and distribution of oleic acid into complex lipids were decreased, while oleic acid oxidation was increased in SENP2-knockdown cells compared to control adipocytes. Furthermore, lipogenesis was reduced by SENP2-knockdown in adipocytes. Although TAG accumulation relative to total uptake was unchanged, there was increased mRNA expression of metabolically relevant genes such as UCP1 and PPARGC1A and mRNA and proteomic data revealed increased levels of mRNA and proteins related to mitochondrial function by SENP2-knockdown. In conclusion, SENP2 is an important regulator of energy metabolism in primary human adipocytes and its knockdown reduce glucose metabolism and lipid accumulation, while increasing lipid oxidation in human adipocytes.

• Dalmao-Fernandez, Andrea; Aizenshtadt, Aleksandra; Bakke, Hege Gilbø; Krauss, Stefan Johannes Karl; Rustan, Arild Christian & Thoresen, G. Hege [Vis alle 7 forfattere av denne artikkelen] (2023). Development of three-dimensional primary human myospheres as culture model of skeletal muscle cells for metabolic studies. Frontiers in Bioengineering and Biotechnology. 11, s. 1–13. doi: 10.3389/fbioe.2023.1130693. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Skeletal muscle is a major contributor to whole-body energy homeostasis and the utilization of fatty acids and glucose. At present, 2D cell models have been the most used cellular models to study skeletal muscle energy metabolism. However, the transferability of the results to in vivo might be limited. This project aimed to develop and characterize a skeletal muscle 3D cell model (myospheres) as an easy and low-cost tool to study molecular mechanisms of energy metabolism. Methods and results: We demonstrated that human primary myoblasts form myospheres without external matrix support and carry structural and molecular characteristics of mature skeletal muscle after 10 days of differentiation. We found significant metabolic differences between the 2D myotubes model and myospheres. In particular, myospheres showed increased lipid oxidative metabolism than the 2D myotubes model, which oxidized relatively more glucose and accumulated more oleic acid. Discussion and conclusion: These analyses demonstrate model differences that can have an impact and should be taken into consideration for studying energy metabolism and metabolic disorders in skeletal muscle.

• Krapf, Solveig; Lund, Jenny; Saqib, Awais Ur Rehman; Bakke, Hege Gilbø; Rustan, Arild Christian & Thoresen, G. Hege [Vis alle 7 forfattere av denne artikkelen] (2022). Pancreatic Cancer Cell-Conditioned, Human-Derived Primary Myotubes Display Increased Leucine Turnover, Increased Lipid Accumulation, and Reduced Glucose Uptake. Metabolites. 12(11). doi: 10.3390/metabo12111095. Fulltekst i vitenarkiv Vis sammendrag

  Metabolic alterations occurring in cancer cells have been seen to also occur in other tissues than cancerous tissue. For instance, cachexia, peripheral insulin resistance, or both are commonly seen in patients with cancer. We explored differences in substrate use in myotubes conditioned with the medium from a pancreatic cancer cell line, PANC-1, or primary human pancreatic cells, hPECs. Protein turnover was assessed using scintillation proximity assay, glucose and oleic acid handling were analyzed by substrate oxidation assay. We performed qPCR to study gene expression and immunoblotting and proteomic analyses to study protein expression. PANC-1-conditioned myotubes had an imbalance in protein turnover with decreased accumulation, increased decay, and decreased MYH2 gene expression. Glucose uptake decreased despite increased insulin-stimulated Akt phosphorylation. Fatty acid uptake increased, whereas fatty acid oxidation was unchanged, leading to accumulation of intracellular lipids (TAG) in PANC-1-conditioned myotubes. Secretome analyses revealed increased release of growth factors and growth factor receptor from PANC-1 cells, potentially affecting muscle cell metabolism. Myotubes exposed to pancreatic cancer cell medium displayed altered energy metabolism with increased protein/leucine turnover and lipid accumulation, while glucose uptake and oxidation reduced. This indicates production and release of substances from pancreatic cancer cells affecting skeletal muscle.

• Mengeste, Abel Mulu; Nikolic, Natasa; Fernandez, Andrea Dalmao; Feng, Yuan Zeng; Nyman, Tuula Anneli & Kersten, Sander [Vis alle 11 forfattere av denne artikkelen] (2022). Insight Into the Metabolic Adaptations of Electrically Pulse-Stimulated Human Myotubes Using Global Analysis of the Transcriptome and Proteome. Frontiers in Physiology. 13. doi: 10.3389/fphys.2022.928195. Fulltekst i vitenarkiv Vis sammendrag

  Electrical pulse stimulation (EPS) has proven to be a useful tool to interrogate cell-specific responses to muscle contraction. In the present study, we aimed to uncover networks of signaling pathways and regulatory molecules responsible for the metabolic effects of exercise in human skeletal muscle cells exposed to chronic EPS. Differentiated myotubes from young male subjects were exposed to EPS protocol 1 (i.e. 2 ms, 10 V, and 0.1 Hz for 24 h), whereas myotubes from middle-aged women and men were exposed to protocol 2 (i.e. 2 ms, 30 V, and 1 Hz for 48 h). Fuel handling as well as the transcriptome, cellular proteome, and secreted proteins of EPS-treated myotubes from young male subjects were analyzed using a combination of high-throughput RNA sequencing, high-resolution liquid chromatography-tandem mass spectrometry, oxidation assay, and immunoblotting. The data showed that oxidative metabolism was enhanced in EPS-exposed myotubes from young male subjects. Moreover, a total of 81 differentially regulated proteins and 952 differentially expressed genes (DEGs) were observed in these cells after EPS protocol 1. We also found 61 overlapping genes while comparing the DEGs to mRNA expression in myotubes from the middle-aged group exposed to protocol 2, assessed by microarray. Gene ontology (GO) analysis indicated that significantly regulated proteins and genes were enriched in biological processes related to glycolytic pathways, positive regulation of fatty acid oxidation, and oxidative phosphorylation, as well as muscle contraction, autophagy/mitophagy, and oxidative stress. Additionally, proteomic identification of secreted proteins revealed extracellular levels of 137 proteins were changed in myotubes from young male subjects exposed to EPS protocol 1. Selected putative myokines were measured using ELISA or multiplex assay to validate the results. Collectively, our data provides new insight into the transcriptome, proteome and secreted proteins alterations following in vitro exercise and is a valuable resource for understanding the molecular mechanisms and regulatory molecules mediating the beneficial metabolic effects of exercise.

• Katare, Parmeshwar Bajirao; Fernandez, Andrea Dalmao; Mengeste, Abel Mulu; Hamarsland, Håvard; Ellefsen, Stian & Bakke, Hege Gilbø [Vis alle 9 forfattere av denne artikkelen] (2022). Energy metabolism in skeletal muscle cells from donors with different body mass index. Frontiers in Physiology. 13. doi: 10.3389/fphys.2022.982842. Fulltekst i vitenarkiv
• Mengeste, Abel Mulu; Katare, Parmeshwar Bajirao; Fernandez, Andrea Dalmao; Lund, Jenny; Bakke, Hege Gilbø & Baker, David [Vis alle 11 forfattere av denne artikkelen] (2022). Knockdown of sarcolipin (SLN) impairs substrate utilization in human skeletal muscle cells. Molecular Biology Reports. ISSN 0301-4851. s. 6005–6017. doi: 10.1007/s11033-022-07387-0. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Recent studies have highlighted that uncoupling of sarco-/endoplasmic reticulum Ca 2+ -ATPase (SERCA) by sarcolipin (SLN) increases ATP consumption and contributes to heat liberation. Exploiting this thermogenic mechanism in skeletal muscle may provide an attractive strategy to counteract obesity and associated metabolic disorders. In the present study, we have investigated the role of SLN on substrate metabolism in human skeletal muscle cells. Methods and results After generation of skeletal muscle cells with stable SLN knockdown (SLN-KD), cell viability, glucose and oleic acid (OA) metabolism, mitochondrial function, as well as gene expressions were determined. Depletion of SLN did not influence cell viability. However, glucose and OA oxidation were diminished in SLN-KD cells compared to control myotubes. Basal respiration measured by respirometry was also observed to be reduced in cells with SLN-KD. The metabolic perturbation in SLN-KD cells was reflected by reduced gene expression levels of peroxisome proliferator-activated receptor γ coactivator 1α ( PGC1α ) and forkhead box O1 ( FOXO1 ). Furthermore, accumulation of OA was increased in cells with SLN-KD compared to control cells. These effects were accompanied by increased lipid formation and incorporation of OA into complex lipids. Additionally, formation of complex lipids and free fatty acid from de novo lipogenesis with acetate as substrate was enhanced in SLN-KD cells. Detection of lipid droplets using Oil red O staining also showed increased lipid accumulation in SLN-KD cells. Conclusions Overall, our study sheds light on the importance of SLN in maintaining metabolic homeostasis in human skeletal muscle. Findings from the current study suggest that therapeutic strategies involving SLN-mediated futile cycling of SERCA might have significant implications in the treatment of obesity and associated metabolic disorders. Graphical abstract

• Krapf, Solveig Astrid; Schjølberg, Tiril; Asoawe, Lucia; Honkanen, Susanna Kyllikki; Kase, Eili Tranheim & Thoresen, G. Hege [Vis alle 7 forfattere av denne artikkelen] (2021). Novel methods for cold exposure of skeletal muscle in vivo and in vitro show temperature-dependent myokine production. Journal of Thermal Biology. ISSN 0306-4565. 98. doi: 10.1016/j.jtherbio.2021.102930. Fulltekst i vitenarkiv Vis sammendrag

  Proteins secreted from skeletal muscle serving a signalling role have been termed myokines. Many of the myokines are exercise factors, produced and released in response to muscle activity. Cold exposures affecting muscle may occur in recreational, occupational and therapeutic settings. Whether muscle temperature independently affects myokine profile, is still to be elucidated. We hypothesized that manipulating muscle temperature by means of external cooling would change myokine production and release. In the present study we have established new models for cold exposure of muscle in vivo and in vitro where rat hind limb or cultured human myotubes were cooled to 18 °C. After a recovery period, muscle tissue, cells and culture media were harvested for further analysis by qPCR and immunoassays. Expression of several myokine genes were significantly increased after cold exposure in both models: in rat muscle, mRNA levels of CCL2 (p = 0.04), VEGFA (p = 0.02), CXCL1 (p = 0.02) and RBM3 (p = 0.02) increased while mRNA levels of IL-6 (p = 0.03) were decreased; in human myotubes, mRNA levels of IL6 (p = 0.01), CXCL8 (p = 0.04), VEGFA (p = 0.03) and CXCL1 (p < 0.01) were significantly increased, as well as intracellular protein levels of IL-8 (CXCL8 gene product; p < 0.01). The corresponding effect on myokine secretion was not observed, on the contrary, IL-8 (p = 0.02) and VEGF (VEGFA gene product) p < 0.01) concentrations in culture media were reduced after cold exposure in vitro. In conclusion, cold exposure of muscle in vivo and in vitro had an effect on the production and release of several known exercise-related myokines. Myokine expression at the level of mRNA and protein was increased by cold exposure, whereas secretion tended to be decreased.

• Skagen, Christine; Nyman, Tuula Anneli; Xiao-Rong, Peng; O'Mahony, Sven; Kase, Eili Tranheim & Rustan, Arild Christian [Vis alle 7 forfattere av denne artikkelen] (2021). Chronic treatment with terbutaline increases glucose and oleic acid oxidation and protein synthesis in cultured human myotubes. Current Research in Pharmacology and Drug Discovery (CRPHAR). 2, s. 1–11. doi: 10.1016/j.crphar.2021.100039. Fulltekst i vitenarkiv
• Mengeste, Abel Mulu; Lund, Jenny; Katare, Parmeshwar Bajirao; Ghobadi, Roya; Bakke, Hege Gilbø & Lunde, Per Kristian [Vis alle 13 forfattere av denne artikkelen] (2021). The small molecule SERCA activator CDN1163 increases energy metabolism in human skeletal muscle cells. Current Research in Pharmacology and Drug Discovery (CRPHAR). 2, s. 1–12. doi: 10.1016/j.crphar.2021.100060. Fulltekst i vitenarkiv
• Lund, Jenny; Krapf, Solveig Astrid; Sistek, Medina; Bakke, Hege Gilbø; Bartesagi, Stefano & Xiao-Rong, Peng [Vis alle 9 forfattere av denne artikkelen] (2021). SENP2 is vital for optimal insulin signaling and insulin-stimulated glycogen synthesis in human skeletal muscle cells. Current Research in Pharmacology and Drug Discovery (CRPHAR). 2, s. 1–10. doi: 10.1016/j.crphar.2021.100061. Fulltekst i vitenarkiv
• Krapf, Solveig Astrid; Lund, Jenny; Lundkvist, Malin; Dale, Marianne Grebstad; Nyman, Tuula Anneli & Thoresen, G. Hege [Vis alle 7 forfattere av denne artikkelen] (2020). Pancreatic cancer cells show lower oleic acid oxidation and their conditioned medium inhibits oleic acid oxidation in human myotubes. Pancreatology (Print). ISSN 1424-3903. 20(4), s. 676–682. doi: 10.1016/j.pan.2020.04.014. Fulltekst i vitenarkiv
• Løvsletten, Nils Gunnar; Vu, Helene Loang Ngo; Skagen, Christine; Lund, Jenny; Kase, Eili Tranheim & Thoresen, G. Hege [Vis alle 8 forfattere av denne artikkelen] (2020). Treatment of human skeletal muscle cells with inhibitors of diacylglycerol acyltransferases 1 and 2 to explore isozyme-specific roles on lipid metabolism. Scientific Reports. 10:238, s. 1–13. doi: 10.1038/s41598-019-57157-5. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Løvsletten, Nils Gunnar; Bakke, Siril Skaret; Kase, Eili Tranheim; Ouwens, D. Margriet; Thoresen, G. Hege & Rustan, Arild (2018). Increased triacylglycerol - Fatty acid substrate cycling in human skeletal muscle cells exposed to eicosapentaenoic acid. PLOS ONE. 13:e0208048(11), s. 1–15. doi: 10.1371/journal.pone.0208048. Fulltekst i vitenarkiv Vis sammendrag

  It has previously been shown that pretreatment of differentiated human skeletal muscle cells (myotubes) with eicosapentaenoic acid (EPA) promoted increased uptake of fatty acids and increased triacylglycerol accumulation, compared to pretreatment with oleic acid (OA) and palmitic acid (PA). The aim of the present study was to examine whether EPA could affect substrate cycling in human skeletal muscle cells by altering lipolysis rate of intracellular TAG and re-esterification of fatty acids. Fatty acid metabolism was studied in human myotubes using a mixture of fatty acids, consisting of radiolabelled oleic acid as tracer (14C-OA) together with EPA or PA. Co-incubation of myotubes with EPA increased cell-accumulation and incomplete fatty acid oxidation of 14C-OA compared to co-incubation with PA. Lipid distribution showed higher incorporation of 14C-OA into all cellular lipids after co-incubation with EPA relative to PA, with most markedly increases (3 to 4-fold) for diacylglycerol and triacylglycerol. Further, the increases in cellular lipids after co-incubation with EPA were accompanied by higher lipolysis and fatty acid re-esterification rate. Correspondingly, basal respiration, proton leak and maximal respiration were significantly increased in cells exposed to EPA compared to PA. Microarray and Gene Ontology (GO) enrichment analysis showed that EPA, related to PA, significantly changed i.e. the GO terms “Neutral lipid metabolic process” and “Regulation of lipid storage”. Finally, an inhibitor of diacylglycerol acyltransferase 1 decreased the effect of EPA to promote fatty acid accumulation. In conclusion, incubation of human myotubes with EPA, compared to PA, increased processes of fatty acid turnover and oxidation suggesting that EPA may activate futile substrate cycling of fatty acids in human myotubes. Increased TAG—FA cycling may be involved in the potentially favourable effects of long-chain polyunsaturated n-3 fatty acids on skeletal muscle and whole-body energy metabolism.

• Lund, Jenny; Helle, Siw A; Li, Yuchuan; Løvsletten, Nils Gunnar; Stadheim, Hans Kristian & Jensen, Jørgen [Vis alle 9 forfattere av denne artikkelen] (2018). Higher lipid turnover and oxidation in cultured human myotubes from athletic versus sedentary young male subjects. Scientific Reports. 8(1). doi: 10.1038/s41598-018-35715-7. Fulltekst i vitenarkiv Vis sammendrag

  In this study we compared fatty acid (FA) metabolism in myotubes established from athletic and sedentary young subjects. Six healthy sedentary (maximal oxygen uptake (VO2max)≤ 46 ml/kg/min) and six healthy athletic (VO2max> 60 ml/kg/min) young men were included. Myoblasts were cultured and diferentiated to myotubes from satellite cells isolated from biopsy of musculus vastus lateralis. FA metabolism was studied in myotubes using [14C]oleic acid. Lipid distribution was assessed by thin layer chromatography, and FA accumulation, lipolysis and re-esterifcation 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, higherTAG-related lipolysis and re-esterifcation, 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 fndings suggestthat cultured myotubes retain some of the phenotypic traits of their donors.

Se alle arbeider i NVA

• Thoresen, G. Hege; Simonsen, terje; Christensen, Hege; Johansen, Harald Thidemann; Kase, Eili Tranheim & Robertsen, Ida [Vis alle 9 forfattere av denne artikkelen] (2021). Basal farmakologi. Fagbokforlaget. ISBN 9788245033557. 405 s. Fulltekst i vitenarkiv
• Thoresen, G. Hege; Solberg, Rigmor; Johansen, Harald Thidemann; Kase, Eili Tranheim; Rustan, Arild Christian & Christensen, Hege [Vis alle 7 forfattere av denne artikkelen] (2020). Illustrert farmakologi. Fagbokforlaget. ISBN 9788245033564. 392 s. Fulltekst i vitenarkiv

Se alle arbeider i NVA