Regulation of energy metabolism in cultured skeletal muscle cells: Effects of exercise, donor differences and perilipin 2. Studies in human and mouse myotubes
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- Farmasøytisk institutt [1937]
Abstract
Exercise can prevent and treat metabolic diseases. This thesis aimed to study energy metabolism in cultured human myotubes from subjects with different metabolic profile and training status, and to study effects of an in vivo exercise intervention on in vitro energy metabolism. Plasma lactate concentrations increase rapidly during exercise, and lactate is an energy source for skeletal muscle. We aimed to study lactate metabolism in cultured human myotubes at rest and to see if lactate exposure affected glucose and lipid metabolism. More than half of the surface area of lipid droplets (LDs) in human muscle biopsies is covered by perilipin 2 (PLIN2). To study the functional role of PLIN2 and LDs on energy metabolism in skeletal muscle we examined myotubes from Plin2+/+ and Plin2-/- mice. Results in this thesis show that exercise is able to induce changes in human myotubes in vivo that are discernible in vitro and that cultured myotubes retain some phenotypic traits of their donors. Ablation of Plin2 shifted cells from glucose to lipid metabolism. Lactate can be stored as glycogen and intracellular lipids in myotubes, and prolonged exposure affected metabolism of glucose and lipids.List of papers
Paper I: 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. Exercise in vivo marks human myotubes in vitro: Training-induced increase in lipid metabolism. PLOS ONE, 2017;12(4):e0175441. The article is included in the file. Also available in DUO: http://hdl.handle.net/10852/59036 |
Paper II: Lund J, Tangen DS, Wiig H, Stadheim HK, Helle SA, Birk JB, Rustan AC, Thoresen GH, Wojtaszewski JFP, Kase ET, and Jensen J. Glucose metabolism and metabolic flexibility in cultured skeletal muscle cells is related to exercise status in young male subjects. Submitted to Archives of Physiology and Biochemistry. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1080/13813455.2017.1369547 |
Paper III: Lund J, Helle SA, Kase ET, Li Y, Løvsletten NG, Stadheim HK, Jensen J, Thoresen GH, and Rustan AC. Higher fatty acid turnover and oxidation in cultured human skeletal muscle cells from trained young male subjects. Submitted to PLOS ONE.The paper is not available in DUO awaiting publishing. |
Paper IV: Lund J, Aas V, Tingstad RH, Van Hees A, and Nikolić N. Lactic acid is readily used as an energy source or stored as glycogen and intracellular lipids in human myotubes. Submitted to PLOS ONE. The paper is not available in DUO awaiting publishing. |
Paper V: Feng YZ, Lund J, Li Y, Knabenes IK, Bakke SS, Kase ET, Lee YK, Kimmel AR, Thoresen GH, Rustan AC, and Dalen KT. Loss of perilipin 2 in cultured myotubes enhances lipolysis and shifts the metabolic energy balance from glucose oxidation towards fatty acid oxidation. Under revision before resubmission to Journal of Lipid Research. The paper is not available in DUO awaiting publishing. |