Carbohydrate metabolism during prolonged exercise and recovery: interactions between pyruvate dehydrogenase, fatty acids, and amino acids

Mourtzakis, Marina; Saltin, Bengt; Graham, Terry E.; Pilegaard, Henriette

doi:10.1152/japplphysiol.00571.2005

Cited by 48 publications

(46 citation statements)

References 39 publications

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“…Previous studies have demonstrated that PGC-1␣ regulates hepatic glucose metabolism by inducing expression of gluconeogenic genes (32)(33)(34)53). Gluconeogenesis is an important source of glucose for skeletal muscle, especially during periods of exertional activity (54). Several lines of evidence shown here support the conclusion that PGC-1␣ also exerts regulatory action directly on muscle to increase glucose availability by augmenting glycogen stores post-exercise through stimulation of glucose import and via "glycogen sparing" effects (Fig.…”

Section: Discussionsupporting

confidence: 72%

A Role for the Transcriptional Coactivator PGC-1α in Muscle Refueling

Wende

Schaeffer

Parker

et al. 2007

Journal of Biological Chemistry

226

239

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The transcriptional coactivator peroxisome proliferator-activated receptor ␥ coactivator-1␣ (PGC-1␣) has been identified as an inducible regulator of mitochondrial function. Skeletal muscle PGC-1␣ expression is induced post-exercise. Therefore, we sought to determine its role in the regulation of muscle fuel metabolism. Studies were performed using conditional, musclespecific, PGC-1␣ gain-of-function and constitutive, generalized, loss-of-function mice. Forced expression of PGC-1␣ increased muscle glucose uptake concomitant with augmentation of glycogen stores, a metabolic response similar to postexercise recovery. Induction of muscle PGC-1␣ expression prevented muscle glycogen depletion during exercise. Conversely, PGC-1␣-deficient animals exhibited reduced rates of muscle glycogen repletion post-exercise. PGC-1␣ 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 ␣. These findings identify PGC-1␣ 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 (1, 2). During acute high intensity exercise, glucose derived from hepatic and muscle glycogen stores serves as the chief energy source (reviewed in Refs. 3-5). 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 (2). 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 (6, 7) (reviewed in Ref. 8).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) 5 -␥ coactivator 1␣ (PGC-1␣), in the regulation of striated muscle energy metabolism and function (9 -13). PGC-1␣ levels are rapidly induced in skeletal muscle following bouts of activity in rodents and humans (14 -22). PGC-1␣ coactivates multiple transcription factors involved in mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation, including the estrogen-related receptor ␣, PPAR␣, and nuclear respiratory factors 1 and 2 (6, 23-26). PGC-1␣ gain-and loss-of-function studies conducted in cells and in mice have demonstrated that PGC-1␣ stimulates gene regulatory programs that augment mitochondrial oxidative capacity in tissues with high energy demands, such as heart and ske...

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Section: Discussionsupporting

confidence: 72%

A Role for the Transcriptional Coactivator PGC-1α in Muscle Refueling

Wende

Schaeffer

Parker

et al. 2007

Journal of Biological Chemistry

226

239

View full text Add to dashboard Cite

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“…Moreover, 82 discrepancies within these human studies, including B-vitamin and subject training status, as 83 well as variations in mode, intensity, and duration of test exercises, limit the strength of their 84 conclusions [16,17]. Mechanistically, reductions in homocysteine concentrations by exercise 85 may be related to increased protein turnover owing to increased plasma methionine 86 concentrations during exercise, followed by reduced concentrations below basal levels after 87 exercise [18][19][20][21]. This fluctuation in methionine availability for methyl group metabolism may 88 be due, in part, to the increased need of methionine for muscle anabolism, potentially resulting in 89 diminished homocysteine production [17,21].…”

mentioning

confidence: 99%

“…Mechanistically, reductions in homocysteine concentrations by exercise 85 may be related to increased protein turnover owing to increased plasma methionine 86 concentrations during exercise, followed by reduced concentrations below basal levels after 87 exercise [18][19][20][21]. This fluctuation in methionine availability for methyl group metabolism may 88 be due, in part, to the increased need of methionine for muscle anabolism, potentially resulting in 89 diminished homocysteine production [17,21]. However, exercise also increases the demand of 90 vitamin B6 to support increased muscle catabolism, thereby potentially limiting its availability 91 for transsulfuration and subsequently resulting in homocysteine accumulation [22].…”

mentioning

confidence: 99%

“…Increased muscle anabolism following exercise may increase the methionine 282 requirement for protein synthesis, thereby limiting its availability for SAM-dependent 283 transmethylation reactions and subsequently decreasing homocysteine production. Alterations in 284 intracellular methionine concentrations owing to exercise have been reported in both animal and 285 human studies [19][20][21][22]. Transsulfuration of homocysteine provides cysteine and α-ketobutyrate, 286 both of which can be utilized in energy production and may have increased importance in 287 supplying the cell with energy during exercise [53].…”

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confidence: 99%

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Exercise prevents hyperhomocysteinemia in a dietary folate-restricted mouse model

Neuman¹,

Albright²,

Schalinske³

2013

Nutrition Research

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Hyperhomocysteinemia is a condition that results from altered methyl group metabolism and is associated with numerous pathological conditions. A number of nutritional and hormonal factors have been shown to influence circulating homocysteine concentrations; however, the impact of exercise on homocysteine and methyl group balance is not well understood. Our hypothesis was that exercise represents an effective means to prevent hyperhomocysteinemia in a folate-independent manner. The purpose of this study was to determine the influence of exercise on homocysteine metabolism in a dietary folate-restricted mouse model characterized by moderate hyperhomocysteinemia. Female outbred mice (12 weeks old) were assigned to either a sedentary or free-access wheel exercise group. Following a 4-week acclimation period, half of the mice in each group were provided a folate-restricted diet for 7-weeks prior to euthanasia and tissue collection. As expected, folate-restricted sedentary mice exhibited a 2-fold increase in plasma total homocysteine concentrations; however, exercise completely prevented the increase in circulating homocysteine concentrations. Moreover, exercise reduced plasma homocysteine concentrations 36% within the group fed only the control diet. The prevention of hyperhomocysteinemia by exercise appears, at least in part, to be the result of increased folate-independent homocysteine remethylation owing to a 2-fold increase in renal betaine homocysteine S-methyltransferase. To our knowledge, this is the first report demonstrating the prevention of hyperhomocysteinemia by exercise in a dietary folate-restriction model. Future research will be directed at determining if exercise can have a positive impact on other nutritional, hormonal, and genetic models of hyperhomocysteinemia relevant to humans. Hyperhomocysteinemia is a condition that results from altered methyl group metabolism and is 30 associated with numerous pathological conditions. A number of nutritional and hormonal factors 31 have been shown to influence circulating homocysteine concentrations; however, the impact of 32 exercise on homocysteine and methyl group balance is not well understood. Our hypothesis was 33 that exercise represents an effective means to prevent hyperhomocysteinemia in a folate-34 independent manner. The purpose of this study was to determine the influence of exercise on 35 homocysteine metabolism in a dietary folate-restricted mouse model characterized by moderate 36 hyperhomocysteinemia. Female outbred mice (12 wk old) were assigned to either a sedentary or 37 free-access wheel exercise group. Following a 4-wk acclimation period, half of the mice in each 38 group were provided a folate-restricted diet for 7-wk prior to euthanasia and tissue collection. As 39 expected, folate-restricted sedentary mice exhibited a 2-fold increase in plasma total 40 homocysteine concentrations; however, exercise completely prevented the increase in circulating 41 homocysteine concentrations. Moreover, exercise reduced plasma homocysteine c...

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“…Some amino acids have important implications for gluconeogenesis and nitrogen balance during and following exercise. Glutamine, glutamate and alanine are gluconeogenic precursors that interlink with pyruvate metabolism and are therefore essential to carbohydrate metabolism (2). An extensive discussion of protein metabolism at rest and during exercise is beyond the scope of this project and for this reason the following chapters will focus only on the contribution of carbohydrate and fat to energy expenditure during and following exercise and the metabolic pathways regulating each.…”

Section: Macronutrients For Energy Productionmentioning

confidence: 99%