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Exercise-induced molecular mechanisms promoting glycogen supercompensation in human skeletal muscle.

ABSTRACT: OBJECTIVE:A single bout of exercise followed by intake of carbohydrates leads to glycogen supercompensation in prior exercised muscle. Our objective was to illuminate molecular mechanisms underlying this phenomenon in skeletal muscle of man. METHODS:We studied the temporal regulation of glycogen supercompensation in human skeletal muscle during a 5 day recovery period following a single bout of exercise. Nine healthy men depleted (day 1), normalized (day 2) and supercompensated (day 5) muscle glycogen in one leg while the contralateral leg served as a resting control. Euglycemic hyperinsulinemic clamps in combination with leg balance technique allowed for investigating insulin-stimulated leg glucose uptake under these 3 experimental conditions. Cellular signaling in muscle biopsies was investigated by global proteomic analyses and immunoblotting. We strengthened the validity of proposed molecular effectors by follow-up studies in muscle of transgenic mice. RESULTS:Sustained activation of glycogen synthase (GS) and AMPK in combination with elevated expression of proteins determining glucose uptake capacity were evident in the prior exercised muscle. We hypothesize that these alterations offset the otherwise tight feedback inhibition of glycogen synthesis and glucose uptake by glycogen. In line with key roles of AMPK and GS seen in the human experiments we observed abrogated ability for glycogen supercompensation in muscle with inducible AMPK deletion and in muscle carrying a G6P-insensitive form of GS in muscle. CONCLUSION:Our study demonstrates that both AMPK and GS are key regulators of glycogen supercompensation following a single bout of glycogen-depleting exercise in skeletal muscle of both man and mouse.

SUBMITTER: Hingst JR

PROVIDER: S-EPMC6158101 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Exercise-induced molecular mechanisms promoting glycogen supercompensation in human skeletal muscle.

Hingst Janne R JR Bruhn Lea L Hansen Mads B MB Rosschou Marie F MF Birk Jesper B JB Fentz Joachim J Foretz Marc M Viollet Benoit B Sakamoto Kei K Færgeman Nils J NJ Havelund Jesper F JF Parker Benjamin L BL James David E DE Kiens Bente B Richter Erik A EA Jensen Jørgen J Wojtaszewski Jørgen F P JFP

Molecular metabolism 20180725

<h4>Objective</h4>A single bout of exercise followed by intake of carbohydrates leads to glycogen supercompensation in prior exercised muscle. Our objective was to illuminate molecular mechanisms underlying this phenomenon in skeletal muscle of man.<h4>Methods</h4>We studied the temporal regulation of glycogen supercompensation in human skeletal muscle during a 5 day recovery period following a single bout of exercise. Nine healthy men depleted (day 1), normalized (day 2) and supercompensated (d ...[more]

PMID: 30093357

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Project description:Compelling evidence has demonstrated the effect of melatonin on exhaustive exercise tolerance and its modulatory role in muscle energy substrates at the end of exercise. In line with this, PGC-1α and NRF-1 also seem to act on physical exercise tolerance and metabolic recovery after exercise. However, the literature still lacks reports on these proteins after exercise until exhaustion for animals treated with melatonin. Thus, the aim of the current study was to determine the effects of acute melatonin administration on muscle PGC-1α and NRF-1, and its modulatory role in glycogen and triglyceride contents in rats subjected to exhaustive swimming exercise at an intensity corresponding to the anaerobic lactacidemic threshold (iLAn). In a randomized controlled trial design, thirty-nine Wistar rats were allocated into four groups: control (CG = 10), rats treated with melatonin (MG = 9), rats submitted to exercise (EXG = 10), and rats treated with melatonin and submitted to exercise (MEXG = 10). Forty-eight hours after the graded exercise test, the animals received melatonin (10 mg/kg) or vehicles 30 min prior to time to exhaustion test in the iLAn (tlim). Three hours after tlim the animals were euthanized, followed by muscle collection for specific analyses: soleus muscles for immunofluorescence, gluteus maximus, red and white gastrocnemius for the assessment of glycogen and triglyceride contents, and liver for the measurement of glycogen content. Student t-test for independent samples, two-way ANOVA, and Newman keuls post hoc test were used. MEXG swam 120.3% more than animals treated with vehicle (EXG; p < 0.01). PGC-1α and NRF-1 were higher in MEXG with respect to the CG (p < 0.05); however, only PGC-1α was higher for MEXG when compared to EXG. Melatonin reduced the triglyceride content in gluteus maximus, red and white gastrocnemius (F = 6.66, F = 4.51, and F = 6.02, p < 0.05). The glycogen content in red gastrocnemius was higher in MEXG than in CG (p = 0.01), but not in EXG (p > 0.05). In conclusion, melatonin was found to enhance exercise tolerance, potentiate exercise-mediated increases in PGC-1α, decrease muscle triglyceride content and increase muscle glycogen 3 h after exhaustive exercise, rapidly providing a better cellular metabolic environment for future efforts.

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Exercise-induced molecular mechanisms promoting glycogen supercompensation in human skeletal muscle.

Publications

Exercise-induced molecular mechanisms promoting glycogen supercompensation in human skeletal muscle.

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