title: Mitochondrial and performance adaptations to exercise training in mice lacking skeletal muscle LKB1.
abstract: LKB1 and its downstream targets of the AMP-activated protein kinase family are important regulators of many aspects of skeletal muscle cell function, including control of mitochondrial content and capillarity. LKB1 deficiency in skeletal and cardiac muscle (mLKB1-KO) greatly impairs exercise capacity. However, cardiac dysfunction in that genetic model prevents a clear assessment of the role of skeletal muscle LKB1 in the observed effects. Our purposes here were to determine whether skeletal muscle-specific knockout of LKB1 (skmLKB1-KO) decreases exercise capacity and mitochondrial protein content, impairs accretion of mitochondrial proteins after exercise training, and attenuates improvement in running performance after exercise training. We found that treadmill and voluntary wheel running capacity was reduced in skmLKB1-KO vs. control (CON) mice. Citrate synthase activity, succinate dehydrogenase activity, and pyruvate dehydrogenase kinase content were lower in KO vs. CON muscles. Three weeks of treadmill training resulted in significantly increased treadmill running performance in both CON and skmLKB1-KO mice. Citrate synthase activity increased significantly with training in both genotypes, but protein content and activity for components of the mitochondrial electron transport chain increased only in CON mice. Capillarity and VEGF protein was lower in skmLKB1-KO vs. CON muscles, but VEGF increased with training only in skmLKB1-KO. Three hours after an acute bout of muscle contractions, PGC-1α, cytochrome c, and VEGF gene expression all increased in CON but not skmLKB1-KO muscles. Our findings indicate that skeletal muscle LKB1 is required for accretion of some mitochondrial proteins but not for early exercise capacity improvements with exercise training.
authors: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah.
authors: Colby B
authors: CB
authors: Tanner
authors: Steven R
authors: SR
authors: Madsen
authors: David M
authors: DM
authors: Hallowell
authors: Darren M J
authors: DM
authors: Goring
authors: Timothy M
authors: TM
authors: Moore
authors: Shalene E
authors: SE
authors: Hardman
authors: Megan R
authors: MR
authors: Heninger
authors: Daniel R
authors: DR
authors: Atwood
authors: David M
authors: DM
authors: Thomson
mesh_terms: D055372:AMP-Activated Protein Kinases; D000222:Adaptation, Physiological; D000818:Animals; D002196:Capillaries / Q000502:physiology; D002950:Citrate (si)-Synthase / Q000378:metabolism; D002952:Citric Acid Cycle; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism*; D009043:Motor Activity; D009048:Motor Skills; D018482:Muscle, Skeletal / Q000098:blood supply / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D013385:Succinate Dehydrogenase; D002950:Citrate (si)-Synthase; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: adenosine 5′-monophosphate-activated prokine kinase; exercise training; liver kinase B1; mitochondria; skeletal muscle
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