title: Remodeling of oxidative energy metabolism by galactose improves glucose handling and metabolic switching in human skeletal muscle cells.
abstract: Cultured human myotubes have a low mitochondrial oxidative potential. This study aims to remodel energy metabolism in myotubes by replacing glucose with galactose during growth and differentiation to ultimately examine the consequences for fatty acid and glucose metabolism. Exposure to galactose showed an increased [(14)C]oleic acid oxidation, whereas cellular uptake of oleic acid uptake was unchanged. On the other hand, both cellular uptake and oxidation of [(14)C]glucose increased in myotubes exposed to galactose. In the presence of the mitochondrial uncoupler carbonylcyanide p-trifluormethoxy-phenylhydrazone (FCCP) the reserve capacity for glucose oxidation was increased in cells grown with galactose. Staining and live imaging of the cells showed that myotubes exposed to galactose had a significant increase in mitochondrial and neutral lipid content. Suppressibility of fatty acid oxidation by acute addition of glucose was increased compared to cells grown in presence of glucose. In summary, we show that cells grown in galactose were more oxidative, had increased oxidative capacity and higher mitochondrial content, and showed an increased glucose handling. Interestingly, cells exposed to galactose showed an increased suppressibility of fatty acid metabolism. Thus, galactose improved glucose metabolism and metabolic switching of myotubes, representing a cell model that may be valuable for metabolic studies related to insulin resistance and disorders involving mitochondrial impairments.
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway. e.t.kase@farmasi.uio.no
authors.forename: Eili Tranheim
authors.initials: ET
authors.lastname: Kase
authors.forename: Nataša
authors.initials: N
authors.lastname: Nikolić
authors.forename: Siril Skaret
authors.initials: SS
authors.lastname: Bakke
authors.forename: Kaja Kamilla
authors.initials: KK
authors.lastname: Bogen
authors.forename: Vigdis
authors.initials: V
authors.lastname: Aas
authors.forename: G Hege
authors.initials: GH
authors.lastname: Thoresen
authors.forename: Arild Christian
authors.initials: AC
authors.lastname: Rustan
mesh_terms: D002250:Carbon Radioisotopes; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects*; D005690:Galactose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects
chemical_list: D002250:Carbon Radioisotopes; D019301:Oleic Acid; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D005947:Glucose; D005690:Galactose
references.citation: Diabetes. 2002 Apr;51(4):921-7
references.pmid: 11916908
references.citation: Diabetes. 2000 Jul;49(7):1169-77
references.pmid: 10909975
references.citation: Diabetes. 2000 May;49(5):677-83
references.pmid: 10905472
references.citation: PLoS One. 2011;6(7):e21068
references.pmid: 21760887
references.citation: J Steroid Biochem Mol Biol. 2012 Feb;128(3-5):154-64
references.pmid: 22051079
references.citation: Biochim Biophys Acta. 2011 Apr;1812(4):423-30
references.pmid: 21172433
references.citation: PLoS One. 2011;6(12):e28536
references.pmid: 22194845
references.citation: Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):698-709
references.pmid: 20226160
references.citation: Pediatr Res. 1977 Oct;11(10 Pt 1):1045-51
references.pmid: 198730
references.citation: Br J Nutr. 2003 Jan;89(1):3-9
references.pmid: 12568659
references.citation: Diabetes Metab J. 2012 Oct;36(5):328-35
references.pmid: 23130316
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683
references.citation: Biochim Biophys Acta. 2012 Feb;1820(2):133-50
references.pmid: 22155143
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: J Lipid Res. 2006 Feb;47(2):366-74
references.pmid: 16301737
references.citation: FEBS J. 2011 Feb;278(3):519-30
references.pmid: 21182590
references.citation: Science. 2009 May 22;324(5930):1029-33
references.pmid: 19460998
references.citation: Cancer Res. 2004 Feb 1;64(3):985-93
references.pmid: 14871829
references.citation: Prog Biophys Mol Biol. 2000;73(2-4):195-262
references.pmid: 10958931
references.citation: Toxicol Sci. 2007 Jun;97(2):539-47
references.pmid: 17361016
references.citation: Biochim Biophys Acta. 2011 Jan;1812(1):94-105
references.pmid: 20888904
references.citation: J Lipid Res. 2007 Apr;48(4):961-7
references.pmid: 17213484
references.citation: Biochim Biophys Acta. 2011 Jun;1807(6):620-5
references.pmid: 21074512
references.citation: J Clin Invest. 2005 Jul;115(7):1934-41
references.pmid: 16007256
references.citation: Biochim Biophys Acta. 1985 Jan 18;844(1):1-8
references.pmid: 3967049
references.citation: Am J Physiol Endocrinol Metab. 2010 Mar;298(3):E602-13
references.pmid: 19996385
references.citation: APMIS. 2001 Nov;109(11):735-44
references.pmid: 11900052
references.citation: J Lipid Res. 2010 Aug;51(8):2090-104
references.pmid: 20363834
references.citation: Prog Lipid Res. 2012 Jan;51(1):36-49
references.pmid: 22120643
references.citation: J Clin Invest. 2005 Jul;115(7):1699-702
references.pmid: 16007246
references.citation: PLoS One. 2012;7(3):e33203
references.pmid: 22457744
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2011 Nov;85(5):227-34
references.pmid: 21549583
references.citation: Diabetes. 2004 Mar;53(3):542-8
references.pmid: 14988236