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      Effects of Oral Resveratrol Supplementation on Glycogen Replenishment and Mitochondria Biogenesis in Exercised Human Skeletal Muscle

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          Abstract

          The present study aimed to investigate the effect of oral resveratrol supplementation on the key molecular gene expressions involved in mitochondria biogenesis and glycogen resynthesis in human skeletal muscle. Nine young male athletes participated in the single-blind and crossover designed study. All subjects completed a 4-day resveratrol and placebo supplement in a randomized order while performing a single bout of cycling exercise. Immediately after the exercise challenge, the subjects consumed a carbohydrate (CHO) meal (2 g CHO/Kg body mass) with either resveratrol or placebo capsules. Biopsied muscle samples, blood samples and expired gas samples were obtained at 0 h and 3 h after exercise. The muscle samples were measured for gene transcription factor expression by real-time PCR for glucose uptake and mitochondria biogenesis. Plasma glucose, insulin, glycerol, non-esterified fatty acid concentrations and respiratory exchange ratio were analyzed during post-exercise recovery periods. The results showed that the muscle glycogen concentrations were higher at 3 h than at 0 h; however, there were no difference between resveratrol trial and placebo trial. There were no significantly different concentrations in plasma parameters between the two trials. Similarly, no measured gene expressions were significant between the two trials. The evidence concluded that the 4-day oral resveratrol supplementation did not improve post-exercise muscle glycogen resynthesis and related glucose uptake and mitochondrial biosynthesis gene expression in men.

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          Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1.

          Mitochondrial number and function are altered in response to external stimuli in eukaryotes. While several transcription/replication factors directly regulate mitochondrial genes, the coordination of these factors into a program responsive to the environment is not understood. We show here that PGC-1, a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells through an induction of uncoupling protein 2 (UCP-2) and through regulation of the nuclear respiratory factors (NRFs). PGC-1 stimulates a powerful induction of NRF-1 and NRF-2 gene expression; in addition, PGC-1 binds to and coactivates the transcriptional function of NRF-1 on the promoter for mitochondrial transcription factor A (mtTFA), a direct regulator of mitochondrial DNA replication/transcription. These data elucidate a pathway that directly links external physiological stimuli to the regulation of mitochondrial biogenesis and function.
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            Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha.

            Diminished mitochondrial oxidative phosphorylation and aerobic capacity are associated with reduced longevity. We tested whether resveratrol (RSV), which is known to extend lifespan, impacts mitochondrial function and metabolic homeostasis. Treatment of mice with RSV significantly increased their aerobic capacity, as evidenced by their increased running time and consumption of oxygen in muscle fibers. RSV's effects were associated with an induction of genes for oxidative phosphorylation and mitochondrial biogenesis and were largely explained by an RSV-mediated decrease in PGC-1alpha acetylation and an increase in PGC-1alpha activity. This mechanism is consistent with RSV being a known activator of the protein deacetylase, SIRT1, and by the lack of effect of RSV in SIRT1(-/-) MEFs. Importantly, RSV treatment protected mice against diet-induced-obesity and insulin resistance. These pharmacological effects of RSV combined with the association of three Sirt1 SNPs and energy homeostasis in Finnish subjects implicates SIRT1 as a key regulator of energy and metabolic homeostasis.
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              Percutaneous needle biopsy of skeletal muscle in physiological and clinical research.

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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                02 December 2020
                December 2020
                : 12
                : 12
                : 3721
                Affiliations
                [1 ]Department of Exercise and Health Sciences, National Taipei University of Nursing and Health Science, Taipei City 112, Taiwan; cchuang@ 123456ntunhs.edu.tw
                [2 ]Department of Physical Education, National Taichung University of Education, Taichung City 403, Taiwan; jamesliu@ 123456gm.ntcu.edu.tw (C.-C.L.); tjp1984@ 123456mail.ntcu.edu.tw (J.-P.T.)
                [3 ]Department of Nutrition, Chung Shan Medical University Hospital, Taichung 404, Taiwan
                [4 ]School of Nutrition, Chung Shan Medical University, Taichung 404, Taiwan
                Author notes
                [* ]Correspondence: clhsu@ 123456csmu.edu.tw (C.-L.H.); ischeng1965@ 123456mail.ntcu.edu.tw (I.-S.C.); Tel.: +886-4-2218-3459 (I.-S.C.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-0315-625X
                Article
                nutrients-12-03721
                10.3390/nu12123721
                7760965
                33276518
                5f729548-0ced-44cc-8355-5319f79fb060
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 October 2020
                : 29 November 2020
                Categories
                Article

                Nutrition & Dietetics
                ergogenic aids,cycling exercise,muscle physiology,energy metabolism
                Nutrition & Dietetics
                ergogenic aids, cycling exercise, muscle physiology, energy metabolism

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