The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) has been identified as an inducible regulator of mitochondrial function. Skeletal muscle PGC-1α expression is induced post-exercise. Therefore, we sought to determine its role in the regulation of muscle fuel metabolism. Studies were performed using conditional, muscle-specific, PGC-1α gain-of-function and constitutive, generalized, loss-of-function mice. Forced expression of PGC-1α increased muscle glucose uptake concomitant with augmentation of glycogen stores, a metabolic response similar to post-exercise recovery. Induction of muscle PGC-1α expression prevented muscle glycogen depletion during exercise. Conversely, PGC-1α-deficient animals exhibited reduced rates of muscle glycogen repletion post-exercise. PGC-1α was shown to increase muscle glycogen stores via several mechanisms including stimulation of glucose import, suppression of glycolytic flux, and by down-regulation of the expression of glycogen phosphorylase and its activating kinase, phosphorylase kinase α. These findings identify PGC-1α as a critical regulator of skeletal muscle fuel stores. The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) has been identified as an inducible regulator of mitochondrial function. Skeletal muscle PGC-1α expression is induced post-exercise. Therefore, we sought to determine its role in the regulation of muscle fuel metabolism. Studies were performed using conditional, muscle-specific, PGC-1α gain-of-function and constitutive, generalized, loss-of-function mice. Forced expression of PGC-1α increased muscle glucose uptake concomitant with augmentation of glycogen stores, a metabolic response similar to post-exercise recovery. Induction of muscle PGC-1α expression prevented muscle glycogen depletion during exercise. Conversely, PGC-1α-deficient animals exhibited reduced rates of muscle glycogen repletion post-exercise. PGC-1α was shown to increase muscle glycogen stores via several mechanisms including stimulation of glucose import, suppression of glycolytic flux, and by down-regulation of the expression of glycogen phosphorylase and its activating kinase, phosphorylase kinase α. These findings identify PGC-1α as a critical regulator of skeletal muscle fuel stores. Glucose and fatty acids are the chief fuel sources for skeletal muscle. During prolonged bouts of low intensity exercise, muscle energy needs are met through utilization of both substrates with mitochondrial fatty acid oxidation serving a “glucose sparing” function (1Hawley J.A. Clin. Exp. Pharmacol. Physiol. 2002; 29: 218-222Crossref PubMed Scopus (202) Google Scholar, 2Holloszy J.O. Kohrt W.M. Hansen P.A. Front. Biosci. 1998; 3: D1011-D1027Crossref PubMed Google Scholar). During acute high intensity exercise, glucose derived from hepatic and muscle glycogen stores serves as the chief energy source (reviewed in Refs. 3Burke L.M. Hawley J.A. Curr. Opin. Clin. Nutr. Metab. Care. 1999; 2: 515-520Crossref PubMed Scopus (36) Google Scholar, 4Coggan A.R. Sports Med. 1991; 11: 102-124Crossref PubMed Scopus (89) Google Scholar, 5Hargreaves M. Proc. Nutr. Soc. 2004; 63: 217-220Crossref PubMed Scopus (45) Google Scholar). Rapid glycogen repletion following a bout of exhausting intense exercise is an important adaptive response, preparing the muscle for subsequent bouts of activity. With endurance exercise training, the capacity for mitochondrial oxidation of fatty acids is augmented and muscle glycogen reserves increase (2Holloszy J.O. Kohrt W.M. Hansen P.A. Front. Biosci. 1998; 3: D1011-D1027Crossref PubMed Google Scholar). In disease states such as diabetes and heart failure, the capacity for muscle energy substrate utilization is reduced due to alterations in glucose metabolism and derangements in mitochondrial function (6Mootha V.K. Lindgren C.M. Eriksson K.-F. Subramanian A. Sihag S. Lehar J. Puigserver P. Carlsson E. Ridderstråle M. Laurila E. Houstis N. Daly M.J. Patterson N. Mesirov J.P. Golub T.R. Tamayo P. Spiegelman B.M. Lander E.S. Hirschhorn J.N. Altshuler D. Groop L.C. Nat. Genet. 2003; 34: 267-273Crossref PubMed Scopus (5971) Google Scholar, 7Mootha V.K. Handschin C. Arlow D. Xie X. St. Pierre J. Sihag S. Yang W. Altshuler D. Puigserver P. Patterson N. Willy P.J. Schulman I.G. Heyman R.A. Lander E.S. Spiegelman B.M. Proc. Natl. Acad. Sci. U. S. A. 2004; 101: 6570-6575Crossref PubMed Scopus (549) Google Scholar) (reviewed in Ref. 8Neubauer S. N. Engl. J. Med. 2007; 356: 1140-1151Crossref PubMed Scopus (1680) Google Scholar). The molecular regulatory mechanisms involved in the control of muscle fuel metabolism are incompletely understood. Recent evidence implicates the transcriptional coactivator, peroxisome proliferator-activated receptor (PPAR) 5The abbreviations used are:PPARperoxisome proliferator-activated receptorPGC-1αperoxisome proliferator-activated receptor γ coactivator-1αPDKpyruvate dehydrogenase kinaseTREtetracycline response elementMCKmuscle creatine kinaseKHBKrebs-Henseleit bicarbonate2-DG2-deoxyglucoseGSglycogen synthaseGSKglycogen synthase kinaseGPhglycogen phosphorylasePhKphosphorylase kinaseRTreverse transcription. 5The abbreviations used are:PPARperoxisome proliferator-activated receptorPGC-1αperoxisome proliferator-activated receptor γ coactivator-1αPDKpyruvate dehydrogenase kinaseTREtetracycline response elementMCKmuscle creatine kinaseKHBKrebs-Henseleit bicarbonate2-DG2-deoxyglucoseGSglycogen synthaseGSKglycogen synthase kinaseGPhglycogen phosphorylasePhKphosphorylase kinaseRTreverse transcription.-γ coactivator 1α (PGC-1α), in the regulation of striated muscle energy metabolism and function (9Lin J. Handschin C. Spiegelman B.M. Cell Metab. 2005; 1: 361-370Abstract Full Text Full Text PDF PubMed Scopus (1651) Google Scholar, 10Finck B.N. Kelly D.P. J. Clin. Investig. 2006; 116: 615-622Crossref PubMed Scopus (1073) Google Scholar, 11Sandri M. Lin J. Handschin C. Yang W. Arany Z.P. Lecker S.H. Goldberg A.L. Spiegelman B.M. Proc. Natl. Acad. Sci. U. S. A. 2006; 103: 16260-16265Crossref PubMed Scopus (739) Google Scholar, 12Gerhart-Hines Z. Rodgers J.T. Bare O. Lerin C. Kim S.H. Mostoslavsky R. Alt F.W. Wu Z. Puigserver P. EMBO J. 2007; 26: 1913-1923Crossref PubMed Scopus (998) Google Scholar, 13Handschin C. Kobayashi Y.M. Chin S. Seale P. Campbell K.P. Spiegelman B.M. Genes Dev. 2007; 21: 770-783Crossref PubMed Scopus (272) Google Scholar). PGC-1α levels are rapidly induced in skeletal muscle following bouts of activity in rodents and humans (14Goto M. Terada S. Kato M. Katoh M. Yokozeki T. Tabata I. Shimokawa T. Biochem. Biophys. Res. Commun. 2000; 274: 350-354Crossref PubMed Scopus (210) Google Scholar, 15Baar K. Wende A.R. Jones T.E. Marison M. Nolte L.A. Chen M. Kelly D.P. Holloszy J.O. FASEB J. 2002; 16: 1879-1886Crossref PubMed Scopus (770) Google Scholar, 16Terada S. Goto M. Kato M. Kawanaka K. Shimokawa T. Tabata I. Biochem. Biophys. Res. Commun. 2002; 296: 350-354Crossref PubMed Scopus (262) Google Scholar, 17Pilegaard H. Saltin B. Neufer P.D. J. Phys. 2003; 546: 851-858Google Scholar, 18Russell A.P. Feilchenfeldt J. Schreiber S. Praz M. Crettenand A. Gobelet C. Meier C.A. Bell D.R. Kralli A. Giacobino J.-P. Dériaz O. Diabetes. 2003; 52: 2874-2881Crossref PubMed Scopus (369) Google Scholar, 19Norrbom J. Sundberg C.J. Ameln H. Kraus W.E. Jansson E. Gustafsson T. J. Appl. Physiol. 2004; 96: 189-194Crossref PubMed Scopus (224) Google Scholar, 20Terada S. Tabata I. Am. J. Physiol. 2004; 286: E208-E216Crossref PubMed Scopus (118) Google Scholar, 21Taylor E.B. Lamb J.D. Hurst R.W. Chesser D.G. Ellingson W.J. Greenwood L.J. Porter B.B. Herway S.T. Winder W.W. Am. J. Physiol. 2005; 289: E960-E968Crossref PubMed Scopus (74) Google Scholar, 22Wende A.R. Huss J.M. Schaeffer P.J. Giguère V. Kelly D.P. Mol. Cell. Biol. 2005; 25: 10684-10694Crossref PubMed Scopus (282) Google Scholar). PGC-1α coactivates multiple transcription factors involved in mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation, including the estrogen-related receptor α, PPARα, and nuclear respiratory factors 1 and 2 (6Mootha V.K. Lindgren C.M. Eriksson K.-F. Subramanian A. Sihag S. Lehar J. Puigserver P. Carlsson E. Ridderstråle M. Laurila E. Houstis N. Daly M.J. Patterson N. Mesirov J.P. Golub T.R. Tamayo P. Spiegelman B.M. Lander E.S. Hirschhorn J.N. Altshuler D. Groop L.C. Nat. Genet. 2003; 34: 267-273Crossref PubMed Scopus (5971) Google Scholar, 23Huss J.M. Kopp R.P. Kelly D.P. J. Biol. Chem. 2002; 277: 40265-40274Abstract Full Text Full Text PDF PubMed Scopus (394) Google Scholar, 24Schreiber S.N. Knutti D. K. T. Kralli A. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, Huss J.M. Kelly D.P. Mol. Cell. Biol. 2000; PubMed Scopus Google Scholar, Z. Puigserver P. U. C. V. A. S. B. Spiegelman B.M. Cell. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). PGC-1α and loss-of-function in and in PGC-1α regulatory mitochondrial oxidative capacity in with high energy such as heart and skeletal muscle A. D. Kelly D.P. J. Clin. Investig. 2000; PubMed Scopus Google Scholar, J. Wu H. Wu Z. O. Puigserver P. E. B.B. R. Spiegelman B.M. 2002; PubMed Scopus Google Scholar, J. Wu J. V.K. S. M. Wu Z. L.M. S. B.B. D. Spiegelman B.M. Cell. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar, C.M. A. M. J.A. Kelly D.P. Res. 2004; PubMed Scopus Google Scholar, B.N. Schaeffer P.J. Wende A.R. S. M. N. C. Chen Z. Holloszy J.O. Kelly D.P. Biol. 2005; 3: Scopus Google Scholar). peroxisome proliferator-activated receptor peroxisome proliferator-activated receptor γ coactivator-1α dehydrogenase kinase response muscle creatine kinase glycogen synthase glycogen synthase kinase glycogen phosphorylase phosphorylase kinase transcription peroxisome proliferator-activated receptor peroxisome proliferator-activated receptor γ coactivator-1α dehydrogenase kinase response muscle creatine kinase glycogen synthase glycogen synthase kinase glycogen phosphorylase phosphorylase kinase transcription as serves as a muscle energy during of high intensity activity. the role of PGC-1α in the control of muscle fatty acid oxidation and mitochondrial respiratory capacity is its to the regulation of skeletal muscle glucose metabolism has been of evidence PGC-1α control muscle glucose metabolism. PGC-1α serves as a regulator of hepatic an important source of substrate for muscle P. J. J. C.J. J. H. D. Spiegelman B.M. 2003; PubMed Scopus Google Scholar, J. Puigserver P. M. Spiegelman B.M. Proc. Natl. Acad. Sci. U. S. A. 2003; PubMed Scopus Google Scholar, J.T. Lerin C. W. Spiegelman B.M. Puigserver P. 2005; PubMed Scopus Google Scholar). PGC-1α has been shown to transcription of the in in Wu Z. Puigserver P. Kelly D.P. Spiegelman B.M. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). PGC-1α expression of the dehydrogenase kinase a regulator of glucose oxidation A.R. Huss J.M. Schaeffer P.J. Giguère V. Kelly D.P. Mol. Cell. Biol. 2005; 25: 10684-10694Crossref PubMed Scopus (282) Google Scholar). In the we sought to the role of PGC-1α in the regulation of muscle fuel metabolism in we an PGC-1α to used in with and PGC-1α-deficient B.N. Schaeffer P.J. Wende A.R. S. M. N. C. Chen Z. Holloszy J.O. Kelly D.P. Biol. 2005; 3: Scopus Google Scholar). of PGC-1α muscle glucose uptake and glycogen levels and prevented depletion of glycogen stores following exercise. glycogen involved several mechanisms including increased capacity for fatty acid oxidation, of glucose and expression to augmentation of muscle glucose import, of and suppression of involved in glycogen and were in with the of for of animals and were and by the Studies of for PGC-1α control of the response C.M. A. M. J.A. Kelly D.P. Res. 2004; PubMed Scopus Google and for the control of the creatine kinase P. R.P. P. C.A. 1998; PubMed Scopus Google Scholar) were and were the was and with St. was of and were performed and were The and of PGC-1α-deficient has been B.N. Schaeffer P.J. Wende A.R. S. M. N. C. Chen Z. Holloszy J.O. Kelly D.P. Biol. 2005; 3: Scopus Google Scholar). were used for with and endurance exercise capacity and glycogen and were to an were to the for 2 to the by for by 1 the of the were for 1 by an increase in of 2 were as the for were to the as the of the were 1 of with 2 of The and increased a of was was increased was as exercise was to exercise and following for glucose and as the were following glycogen were with a glucose 1 of of following of the exercise and by of exercise. The were and in for glycogen and and was was used for dehydrogenase were in and with acid was in and in in were with and for and was from using the with were performed using was performed as J.M. I. B. Giguère V. Kelly D.P. Mol. Cell. Biol. 2004; PubMed Scopus Google Scholar) and were to the expression of used for in were by and to was performed using and a from J.M. J. Holloszy J.O. M. J. Biol. Chem. Full Text PDF PubMed Google to from P.J. J. Biol. Chem. Full Text PDF PubMed Google from Biochem. J. 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Spiegelman B.M. 2002; PubMed Scopus Google expression of PGC-1α increased of the muscle of the of expression dehydrogenase in with an increase in of oxidative in muscle the and PGC-1α in skeletal was Forced expression of PGC-1α in a increase in the of muscle from animals exhibited with and glycogen an increase in fuel stores function were performed from of and mice. as rates were in from the In the of was in both and the of the was to In to the with rates with were the The activity of the acid synthase and the expression of nuclear and mitochondrial involved in mitochondrial fatty acid and oxidative were increased in the muscle of the of the fatty acid was induced in the muscle of PGC-1α the capacity for muscle mitochondrial fatty acid PGC-1α Glucose and sought to the of PGC-1α muscle glucose metabolism. of uptake were in from and mice. uptake rates in muscle were with control with the glucose uptake expression of and was induced in muscle of the determine the of the glucose rates were in skeletal muscle by following the of from PGC-1α to a in glycolytic The glycolytic was with a in the expression of the a in the glycolytic we PGC-1α glucose oxidation by expression of the a regulator of the dehydrogenase A.R. Huss J.M. Schaeffer P.J. Giguère V. Kelly D.P. Mol. Cell. Biol. 2005; 25: 10684-10694Crossref PubMed Scopus (282) Google Scholar). with the shown PGC-1α and glucose The increased rates of muscle glucose uptake with glycolytic in the the glucose was to with levels of were increased is to increase glycogen glycogen levels were by acid acid was increased in muscle with of muscle glycogen levels were in muscle with control muscle expression of PGC-1α and muscle glycogen stores through the of increased glucose and down-regulation of glycolytic Forced of PGC-1α of during derived from muscle and hepatic glycogen is a critical source of fuel for muscle. exercise, glycogen stores are rapidly (2Holloszy J.O. Kohrt W.M. Hansen P.A. Front. Biosci. 1998; 3: D1011-D1027Crossref PubMed Google Scholar, 5Hargreaves M. Proc. Nutr. Soc. 2004; 63: 217-220Crossref PubMed Scopus (45) Google Scholar). we shown PGC-1α levels are induced in skeletal muscle post-exercise A.R. Huss J.M. Schaeffer P.J. Giguère V. Kelly D.P. Mol. Cell. Biol. 2005; 25: 10684-10694Crossref PubMed Scopus (282) Google Scholar). the of the response, muscle glycogen levels were and exhausting exercise. the of muscle PGC-1α expression was induced in to low intensity exhausting muscle glycogen levels were increased following of PGC-1α expression in the was in the exercise, muscle glycogen levels were reduced in levels in the glycogen was in both to a in animals sought to the of a high intensity exercise is to increase of skeletal muscle and (reviewed in Ref. Biochem. Physiol. 1998; Scopus Google Scholar). glycolytic is in was exercise in the with the low intensity high intensity exhausting exercise muscle glycogen in In levels were and following exercise in the with with reduced glycolytic the high intensity exercise a for with control animals These evidence PGC-1α and glycogen stores. function is adaptive during the post-exercise expression of PGC-1α and during intense exercise by muscle glycogen and glucose PGC-1α for determine PGC-1α is for glycogen in skeletal we PGC-1α-deficient B.N. Schaeffer P.J. Wende A.R. S. M. N. C. Chen Z. Holloszy J.O. Kelly D.P. Biol. 2005; 3: Scopus Google Scholar). muscle glycogen levels were and following low intensity exhausting exercise in and control glycogen levels were in the PGC-1α is for muscle glycogen sought to the of exercise. we shown B.N. Schaeffer P.J. Wende A.R. S. M. N. C. Chen Z. Holloszy J.O. Kelly D.P. Biol. 2005; 3: Scopus Google exhibited reduced exercise capacity the muscle glycogen levels were to levels in both control and animals the of post-exercise of muscle glycogen in the animals animals These findings are with a for PGC-1α in the of glycogen post-exercise. The in skeletal muscle glycogen rates in the due to glucose to a in glucose glucose levels were and the of exercise in the and was in glucose levels the glucose levels were in the mice. levels were in the mice. by the in the levels were in the muscle of These capacity for muscle glucose uptake to the in post-exercise glycogen in the mice. PGC-1α the levels are by the of glucose substrate and the glycogen and The of the glycogen and are by and (reviewed in Ref. P.J. Curr. Mol. Med. 2002; 2: PubMed Scopus Google Scholar). in to substrate the of PGC-1α of glycogen levels involved regulation of the glycogen glycogen synthase and glycogen phosphorylase of the activity of the of expression and through control via activating phosphorylation, of in the by glycogen synthase is to its activity J.N. Proc. Nutr. Soc. 2004; 63: PubMed Scopus Google Scholar). levels and of its were in and The expression and of and were In levels were and levels were such the was reduced to of control in the muscle These to activity of glycogen during exercise of by phosphorylase kinase is with the of levels of were reduced in the muscle of is by stimulation with the muscle glycogen levels are in during exercise. levels of both and were reduced the down-regulation of by PGC-1α in the of expression These identify an PGC-1α serves to muscle glycogen via of glycogen the role of PGC-1α in the control of muscle energy metabolism in we an skeletal PGC-1α we of PGC-1α expression muscle a oxidative gain-of-function and loss-of-function PGC-1α muscle glucose metabolism. PGC-1α hepatic glucose metabolism by expression of P. J. J. C.J. J. H. D. Spiegelman B.M. 2003; PubMed Scopus Google Scholar, J. Puigserver P. M. Spiegelman B.M. Proc. Natl. Acad. Sci. U. S. A. 2003; PubMed Scopus Google Scholar, J.T. Lerin C. W. Spiegelman B.M. Puigserver P. 2005; PubMed Scopus Google Scholar, S. S. R. A. D. C. Puigserver P. Spiegelman B. M. PubMed Scopus Google Scholar). is an important source of glucose for skeletal during of activity M. Saltin B. T. H. J. Appl. Physiol. 2006; PubMed Scopus Google Scholar). of evidence shown the PGC-1α regulatory muscle to increase glucose by glycogen stores post-exercise through stimulation of glucose and via sparing” we muscle glucose uptake is increased in muscle. These are with the PGC-1α expression of the in muscle Wu Z. Puigserver P. Kelly D.P. Spiegelman B.M. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). Forced expression of PGC-1α a increase in and in the of increased glucose PGC-1α in suppression of muscle glycolytic rates as by of glycolytic and of In we shown PGC-1α glucose oxidation by expression A.R. Huss J.M. Schaeffer P.J. Giguère V. Kelly D.P. Mol. Cell. Biol. 2005; 25: 10684-10694Crossref PubMed Scopus (282) Google Scholar). of and glucose oxidation the for of glucose to PGC-1α regulatory glycogen an important for glycogen in muscle. increased levels of a in the glycogen P.J. Curr. Mol. Med. 2002; 2: PubMed Scopus Google Scholar, J.N. 2003; Scholar). PGC-1α was shown to levels and of the for glycogen During the of P. E. N. Am. J. Physiol. 2006; Scholar) of PGC-1α increased expression and glycogen in with the of the in In by M. K. A. 2005; PubMed Scopus Google Scholar) a role for in glycogen in hepatic glucose is an important source of glucose for skeletal muscle. The of the PGC-1α is of muscle glucose uptake and glycogen stores. The of the are with the a of a of hepatic glucose to the reduced of muscle glycogen post-exercise hepatic glucose from has been shown to reduced in the Wende A.R. Chen Z. B.N. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). several of evidence the muscle PGC-1α to the we as by the muscle levels are reduced in the mice. is serves as the chief source of glucose from during exercise R. J. Clin. Metab. 2004; PubMed Scopus Google Scholar, N. J. Appl. Physiol. 2002; PubMed Scopus (45) Google Scholar). hepatic capacity is reduced in glycogen stores and rates are increased Wende A.R. Chen Z. B.N. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). glucose levels were to increased in post-exercise. we the muscle glycogen in reduced capacity for muscle glucose uptake and glycogen with the gain-of-function to by hepatic glucose by using PGC-1α is the of PGC-1α muscle glucose metabolism are by both and regulatory expression of PGC-1α increased the expression of and shown PGC-1α transcription via the transcription Wu Z. Puigserver P. Kelly D.P. Spiegelman B.M. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). for the of and expression we shown PGC-1α transcription by the nuclear receptor estrogen-related receptor A.R. Huss J.M. Schaeffer P.J. Giguère V. Kelly D.P. Mol. Cell. Biol. 2005; 25: 10684-10694Crossref PubMed Scopus (282) Google Scholar). the of glucose uptake and of glucose oxidation of PGC-1α transcription the mechanisms involved in and are The of is involved in the of glycolytic flux, a in shown of PPARα, a of to down-regulation of expression B.N. C. T. N. Holloszy J.O. Kelly D.P. Cell Metab. 2005; 1: Full Text Full Text PDF PubMed Scopus Google Scholar). PGC-1α are transcriptional is to the is the mechanisms involved in of expression and its activating kinase the mechanisms involved in has been shown to increase muscle mitochondrial and capacity for muscle fatty acid oxidation (1Hawley J.A. Clin. Exp. Pharmacol. Physiol. 2002; 29: 218-222Crossref PubMed Scopus (202) Google Scholar, 2Holloszy J.O. Kohrt W.M. Hansen P.A. Front. Biosci. 1998; 3: D1011-D1027Crossref PubMed Google Scholar, J.O. J. Appl. Physiol. PubMed Scopus Google are by expression of PGC-1α (9Lin J. Handschin C. Spiegelman B.M. Cell Metab. 2005; 1: 361-370Abstract Full Text Full Text PDF PubMed Scopus (1651) Google Scholar, 10Finck B.N. Kelly D.P. J. Clin. Investig. 2006; 116: 615-622Crossref PubMed Scopus (1073) Google Scholar, J. Wu H. Wu Z. O. Puigserver P. E. B.B. R. Spiegelman B.M. 2002; PubMed Scopus Google Scholar, P. J. 2005; 29: PubMed Scopus Google Scholar). exercise muscle glucose metabolism in the post-exercise including an increase in muscle glycogen stores and a in energy substrate utilization from to fatty acid The PGC-1α is and for of muscle post-exercise. PGC-1α expression of and of has been shown to by exercise FASEB J. PubMed Scopus Google Scholar, T. S. P.J. M. Holloszy J.O. A. J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. Saltin B. J. Appl. Physiol. PubMed Scopus Google Scholar, J.A. R.A. R. H. L.J. Am. J. Physiol. 1998; 274: Google Scholar, D.P. J. Appl. Physiol. PubMed Scopus Google Scholar). levels of PGC-1α to reduced of a critical of glycogen during of increased such as with exercise. with glycogen levels were during exercise in mice. glucose uptake with suppression of and glycogen by PGC-1α to an increase in the glycogen fuel in a similar to of endurance we increased in the of increased fuel to exercise the of with to intense exercise the of the of PGC-1α post-exercise is exhibited exercise with reduced and in glycogen with of the source of energy during intense exercise. The of PGC-1α for regulation of response (14Goto M. Terada S. Kato M. Katoh M. Yokozeki T. Tabata I. Shimokawa T. Biochem. Biophys. Res. Commun. 2000; 274: 350-354Crossref PubMed Scopus (210) Google Scholar, 15Baar K. Wende A.R. Jones T.E. Marison M. Nolte L.A. Chen M. Kelly D.P. Holloszy J.O. FASEB J. 2002; 16: 1879-1886Crossref PubMed Scopus (770) Google Scholar, 22Wende A.R. Huss J.M. Schaeffer P.J. Giguère V. Kelly D.P. Mol. Cell. Biol. 2005; 25: 10684-10694Crossref PubMed Scopus (282) Google Scholar, A. D. Kelly D.P. J. Clin. Investig. 2000; PubMed Scopus Google Scholar, P. Wu Z. R. M. Spiegelman B.M. Cell. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). Skeletal muscle is a of glucose has been molecular regulatory by exercise a the of heart failure, and (reviewed in Ref. F.W. J. Physiol. 2002; PubMed Scopus Google Scholar). the of and diabetes is with muscle substrate N. Acad. Sci. 2002; PubMed Scopus Google Scholar) and an and reduced levels of muscle PGC-1α has been shown by several (6Mootha V.K. Lindgren C.M. Eriksson K.-F. Subramanian A. Sihag S. Lehar J. Puigserver P. Carlsson E. Ridderstråle M. Laurila E. Houstis N. Daly M.J. Patterson N. Mesirov J.P. Golub T.R. Tamayo P. Spiegelman B.M. Lander E.S. Hirschhorn J.N. Altshuler D. Groop L.C. Nat. Genet. 2003; 34: 267-273Crossref PubMed Scopus (5971) Google Scholar, S. K. R. S. I. M. R. E. R. J. L.J. Proc. Natl. Acad. Sci. U. S. A. 2003; PubMed Scopus Google Scholar). the of reduced muscle PGC-1α to to mitochondrial function derangements in glucose and glycogen metabolism are muscle glucose uptake and glycogen metabolic by PGC-1α and glucose oxidation, are by the of PGC-1α muscle glucose in of by increased expression of glucose and is with the of exercise glucose in an T. S. P.J. M. Holloszy J.O. A. J. Biol. Chem. Full Text PDF PubMed Google Scholar). In an role for the inducible transcriptional coactivator In to oxidative metabolism in PGC-1α is of metabolic involved in the of muscle a source of fuel for muscle during of intense activity. are to for the and and for to for and for critical of the and for with for in preparing with
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