Glucose ingestion during exercise blunts exercise-induced gene expression of skeletal muscle fat oxidative genes

Civitarese, Anthony E.; Hesselink, Matthijs K. C.; Russell, Aaron P.; Ravussin, Éric; Schrauwen, Patrick

doi:10.1152/ajpendo.00193.2005

Cited by 85 publications

(88 citation statements)

References 47 publications

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“…For example, in healthy subjects, the acute exercise-induced activation of the signaling kinases AMPK (60, 62) and p38MAPK (8, 12) are greater when preexercise glycogen availability is low. Transcription of several metabolic related genes such as PDK4, CPT-1, CD36, GLUT-4, UCP-3, and HSP72 are also enhanced when exercise is completed with reduced CHO availability before and/or during exercise (9,11,13,43). Furthermore, we (32) and others (15,21,54,63) have demonstrated that chronic exercise (i.e., endurance training) deliberately commenced with reduced endogenous and exogenous carbohydrate availability results in enhanced skeletal muscle oxidative capacity.…”

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confidence: 61%

Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis

Bartlett

Louhelainen

Iqbal

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

128

160

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Bartlett JD, Louhelainen J, Iqbal Z, Cochran AJ, Gibala MJ, Gregson W, Close GL, Drust B, Morton JP. Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis. Am J Physiol Regul Integr Comp Physiol 304: R450 -R458, 2013. First published January 30, 2013 doi:10.1152/ajpregu.00498.2012The mechanisms that regulate the enhanced skeletal muscle oxidative capacity observed when training with reduced carbohydrate (CHO) availability are currently unknown. The aim of the present study was to test the hypothesis that reduced CHO availability enhances p53 signaling and expression of genes associated with regulation of mitochondrial biogenesis and substrate utilization in human skeletal muscle. In a repeated-measures design, muscle biopsies (vastus lateralis) were obtained from eight active males before and after performing an acute bout of high-intensity interval running with either high (HIGH) or low CHO availability (LOW). Resting muscle glycogen (HIGH, 467 Ϯ 19; LOW, 103 Ϯ 9 mmol/kg dry wt) was greater in HIGH compared with LOW (P Ͻ 0.05). Phosphorylation (P-) of ACC Ser79 (HIGH, 1.4 Ϯ 0.4; LOW, 2.9 Ϯ 0.9) and p53 Ser15 (HIGH, 0.9 Ϯ 0.4; LOW, 2.6 Ϯ 0.8) was higher in LOW immediately postexercise and 3 h postexercise, respectively (P Ͻ 0.05). Before and 3 h postexercise, mRNA content of pyruvate dehydrogenase kinase 4, mitochondrial transcription factor A, cytochrome-c oxidase IV, and PGC-1␣ were greater in LOW compared with HIGH (P Ͻ 0.05), whereas carnitine palmitoyltransferase-1 showed a trend toward significance (P ϭ 0.09). However, only PGC-1␣ expression was increased by exercise (P Ͻ 0.05), where three-fold increases occurred independently of CHO availability. We conclude that the exerciseinduced increase in p53 phosphorylation is enhanced in conditions of reduced CHO availability, which may be related to upstream signaling through AMPK. Given the emergence of p53 as a molecular regulator of mitochondrial biogenesis, such nutritional modulation of contraction-induced p53 activation has implications for both athletic and clinical populations.AMPK; PGC-1␣; glycogen; high-intensity interval running SKELETAL MUSCLE MITOCHONDRIAL biogenesis is one of the most prominent adaptations induced by endurance exercise training (20). At a molecular level, mitochondrial adaptations to exercise are thought to be due to the cumulative effects of the transient increases in the transcripts of mRNA that encode the upregulation of mitochondrial proteins (37). In considering possible contractile induced stressors for activating the acute cell signaling pathways associated with regulation of mitochondrial biogenesis, reductions in carbohydrate (CHO) availability is now emerging as one of the most potent signals (41). For example, in healthy subjects, the acute exercise-induced activation of the signaling kinases AMPK (60, 62) and p38MAPK (8, 12) are greater when preexercise glycogen availability is low. Transcription of several metabolic related genes ...

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confidence: 61%

Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis

Bartlett

Louhelainen

Iqbal

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

128

160

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“…Intracellular messengers during muscle contraction (calcium, ADP, AMP, cAMP, Pi) induce upregulation of several upstream proteins such as AMP-activated protein kinase (AMPK) and peroxisome proliferator receptor gamma coactivator-1 alpha (PGC-1 ) (Civitarese et al 2007(Civitarese et al , 2005Freyssenet 2007). PGC-1 lies upstream of the nuclear respiratory factors (NRF) 1 and 2 and mitochondrial transcription factor A (TFAM) which regulates both the genomic and mitochondrial gene expression involved in mitochondrial adaptation (Civitarese et al 2007;Hood et al 2006;Wright et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Successive bouts of cycling stimulates genes associated with mitochondrial biogenesis

et al. 2009

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Exercise increases mRNA for genes involved in mitochondrial biogenesis and oxidative enzyme capacity. However, little is known about how these genes respond to consecutive bouts of prolonged exercise. We examined the effects of 3 h of intensive cycling performed on three consecutive days on the mRNA associated with mitochondrial biogenesis in trained human subjects. Forty trained cyclists were tested for VO(2max) (54.7 +/- 1.1 ml kg(-1) min(-1)). The subjects cycled at 57% watts(max) for 3 h using their own bicycles on CompuTrainer Pro Model trainers (RacerMate, Seattle, WA) on three consecutive days. Muscle biopsies were obtained from the vastus lateralis pre- and post-exercise on days one and three. Muscle samples were analyzed for mRNA content of peroxisome proliferator receptor gamma coactivator-1 alpha (PGC-1alpha), sirtuin 1 (Sirt-1), cytochrome c, and citrate synthase. Data were analyzed using a 2 (time) x 2 (day) repeated measures ANOVA. Of the mRNA analyzed, the following increased from pre to post 3 h rides: cytochrome c (P = 0.006), citrate synthase (P = 0.03), PGC-1alpha (P < 0.001), and Sirt-1 (P = 0.005). The following mRNA showed significant effects from days one to three: cytochrome c (P < 0.001) and citrate synthase (P = 0.01). These data show that exhaustive cycling performed on three consecutive days resulted in both acute and chronic stimuli for mRNA associated with mitochondrial biogenesis in already trained subjects. This is the first study to illustrate an increase in sirtuin-1 mRNA with acute and chronic exercise. These data contribute to the understanding of mRNA expression during both acute and successive bouts of prolonged exercise.

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“…However, it is still unclear whether these adaptations are specifically due to the increased FFA supply per se or result from decreased glucose availability. Omission of glucose ingestion during exercise also stimulates FFA oxidation rate and upregulates genes involved in fat metabolism such as carnitine palmitoyltransferase I and FAT/CD36 (13,14).Fasting is a specific nutritional condition for stimulating FFA supply, relative to carbohydrate supply, to muscles during exercise. The elevated plasma adrenaline-to-insulin ratio, due to fasting, increases circulating FFA concentration via stimulation of peripheral lipolysis (3,19,23).…”

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confidence: 99%

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confidence: 99%

High-fat diet overrules the effects of training on fiber-specific intramyocellular lipid utilization during exercise

Proeyen

Szlufcik

Nielens

et al. 2011

Journal of Applied Physiology

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Van Proeyen K, Szlufcik K, Nielens H, Deldicque L, Van Dyck R, Ramaekers M, Hespel P. High-fat diet overrules the effects of training on fiber-specific intramyocellular lipid utilization during exercise. J Appl Physiol 111: 108 -116, 2011. First published May 5, 2011 doi:10.1152/japplphysiol.01459.2010In this study, we compared the effects of endurance training in the fasted state (F) vs. the fed state [ample carbohydrate intake (CHO)] on exercise-induced intramyocellular lipid (IMCL) and glycogen utilization during a 6-wk period of a hypercaloric (ϳϩ30% kcal/day) fat-rich diet (HFD; 50% of kcal). Healthy male volunteers (18 -25 yrs) received a HFD in conjunction with endurance training (four times, 60 -90 min/wk) either in F (n ϭ 10) or with CHO before and during exercise sessions (n ϭ 10). The control group (n ϭ 7) received a HFD without training and increased body weight by ϳ3 kg (P Ͻ 0.001). Before and after a HFD, the subjects performed a 2-h constant-load bicycle exercise test in F at ϳ70% maximal oxygen uptake rate. A HFD, both in the absence (F) or presence (CHO) of training, elevated basal IMCL content by ϳ50% in type I and by ϳ75% in type IIa fibers (P Ͻ 0.05). Independent of training in F or CHO, a HFD, as such, stimulated exercise-induced net IMCL breakdown by approximately twofold in type I and by approximately fourfold in type IIa fibers. Furthermore, exercise-induced net muscle glycogen breakdown was not significantly affected by a HFD. It is concluded that a HFD stimulates net IMCL degradation by increasing basal IMCL content during exercise in type I and especially IIa fibers. Furthermore, a hypercaloric HFD provides adequate amounts of carbohydrates to maintain high muscle glycogen content during training and does not impair exercise-induced muscle glycogen breakdown. skeletal muscle; fasted exercise; fat-rich feeding; energy substrate metabolism; muscle lipids IT IS WELL ESTABLISHED THAT dietary factors play an important role in modulating the acute and chronic metabolic responses to endurance exercise (30). In this regard, increased preexercise dietary fat supply stimulates energy provision via fat oxidation during exercise (8,33). By analogy, fatty acid infusion elevates the input of free fatty acids (FFAs) in the energy substrate mix fueling muscle contractions (22, 48a, 49). Furthermore, chronic exposure to a high-fat diet (HFD) also enhances the use of FFAs in endurance exercise (8,9,25,29,(32)(33)(34)58). This is, at least partly, due to upregulation of rate-limiting steps in fat metabolic pathways. Thus FFA oxidation can be stimulated with appropriate chronic exercise and/or nutrition (e.g., HFD), which upregulates pivotal steps in FFA catabolism such as fatty acid translocase (FAT)/CD36 (4, 9), ␤-hydroxyacyl CoA dehydrogenase (␤-HAD) (9, 31), and hormone-sensitive lipase (HSL) (58). However, it is still unclear whether these adaptations are specifically due to the increased FFA supply per se or result from decreased glucose availability. Omission of glucose ingestion during exercise a...

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Glucose ingestion during exercise blunts exercise-induced gene expression of skeletal muscle fat oxidative genes

Cited by 85 publications

References 47 publications

Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis

Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis

Successive bouts of cycling stimulates genes associated with mitochondrial biogenesis

High-fat diet overrules the effects of training on fiber-specific intramyocellular lipid utilization during exercise

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