Training state and fasting-induced PDH regulation in human skeletal muscle
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The aim of the present study was to examine the influence of training state on fasting-induced skeletal muscle pyruvate dehydrogenase (PDH) regulation, including PDH phosphorylation. Trained and untrained subjects, matched for skeletal muscle CS activity and OXPHOS protein, fasted for 36 h after receiving a standardized meal. Respiratory exchange ratio (RER) was measured and blood as well as vastus lateralis muscle biopsies were obtained 2, 12, 24, and 36 h after the meal. RER decreased with fasting only in untrained individuals, while PDHa activity decreased from 12 h after the meal in untrained, but only tended to decrease at 36 h in trained. PDH-E1α, PDP1 protein, PDH phosphorylation, and PDH acetylation in skeletal muscle was higher in trained than untrained subjects, but did not change with fasting, while PDK4 protein was higher at 36 h than at 2 h after the meal in both groups. In conclusion, the present results suggest that endurance exercise training modifies the fasting-induced regulation of PDHa activity in skeletal muscle and the substrate switch towards fat oxidation. PDH phosphorylation could not explain the fasting-induced regulation of PDHa activity suggesting other post translational modifications.
KeywordsPyruvate dehydrogenase Skeletal muscle Acetylation Phosphorylation Fasting Exercise training
We would like to thank the involved subjects for participation in the study.
This study was funded by the Danish Ministry of Culture for Sports Research (1095421001), the Danish Council for Independent Research (36723-104353), and the Danish Diabetes Academy (1105701001). The Centre for Physical Activity Research is supported by a grant from TrygFonden, and the Centre of Inflammation and Metabolism was supported by a grant from the Danish National Research Foundation (DNRF55).
- 17.Fan J, Shan C, Kang HB, Elf S, Xie J, Tucker M, Gu TL, Aguiar M, Lonning S, Chen H, Mohammadi M, Britton LM, Garcia BA, Aleckovic M, Kang Y, Kaluz S, Devi N, Van Meir EG, Hitosugi T, Seo JH, Lonial S, Gaddh M, Arellano M, Khoury HJ, Khuri FR, Boggon TJ, Kang S, Chen J (2014) Tyr phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to regulate the pyruvate dehydrogenase complex. Mol Cell 53:534–548CrossRefPubMedCentralGoogle Scholar
- 18.Frayn KN (1983) Calculation of substrate oxidation rates in vivo from gaseous exchange. Physiol Rep 55:628–634Google Scholar
- 22.Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard DB, Grueter CA, Harris C, Biddinger S, Ilkayeva OR, Stevens RD, Li Y, Saha AK, Ruderman NB, Bain JR, Newgard CB, Farese RV Jr, Alt FW, Kahn CR, Verdin E (2010) SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464:121–125CrossRefPubMedCentralGoogle Scholar
- 25.Kiilerich K, Adser H, Jakobsen AH, Pedersen PA, Hardie DG, Wojtaszewski JF, Pilegaard H (2010) PGC-1alpha increases PDH content but does not change acute PDH regulation in mouse skeletal muscle. Am J Phys Regul Integr Comp Phys 299:R1350–R1359Google Scholar
- 29.Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis M, Guarente LP, Farese RV Jr, Weissman S, Verdin E, Schwer B (2007) Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol 27:8807–8814CrossRefPubMedCentralGoogle Scholar
- 30.Lowry OH, Passonneau JV (1972) A flexible system of enzymatic analysis. Academic Press, New YorkGoogle Scholar
- 41.Sugden MC, Kraus A, Harris RA, Holness MJ (2000) Fibre-type specific modification of the activity and regulation of skeletal muscle pyruvate dehydrogenase kinase (PDK) by prolonged starvation and refeeding is associated with targeted regulation of PDK isoenzyme 4 expression. Biochem J 346 Pt 3:651–657CrossRefPubMedCentralGoogle Scholar