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Red grape leaf extract improves endurance capacity by facilitating fatty acid utilization in skeletal muscle in mice

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Abstract

Improving endurance capacity leads to increased athletic performance and active lifestyles. The aim of this study was to investigate the effect of the intake of red grape leaf extract (RGLE), used as a traditional herbal medicine in the Mediterranean area, on endurance capacity in mice. Male BALB/c mice were divided into three experimental groups with similar swimming times and body weights; control group, 0.2% (w/w) and 0.5% RGLE group. Swimming times were measured for evaluation of endurance capacity once a week during the 10-week experimental period. Blood and tissues were collected from anesthetized mice immediately after 30 min of swimming exercise, and analyzed blood component and fatty acid oxidation enzyme activity, and gene expression in soleus muscle and mesenteric adipose tissue. Endurance capacity was improved by RGLE in a dose-related manner, and was significantly longer in the 0.5% RGLE group than in the control group at week 10. Plasma lactate levels after exercise in the 0.5% RGLE group were significantly lower than that in the control group. RGLE induced the upregulation of hormone-sensitive lipase mRNA in mesenteric adipose tissue, increased the plasma free fatty acid concentration after exercise, and enhanced fatty acid oxidation enzyme activity in the soleus muscle. Furthermore, peroxisome proliferator-activated receptor-gamma coactivator 1α (Pgc1α) and its downstream target genes were also significantly upregulated in the soleus muscle in the 0.5% RGLE group. Intake of RGLE upregulated Pgc1α expression and facilitated fatty acid oxidation in skeletal muscle, and these effects contributed, in part, to improve endurance capacity.

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References

  • Albright A, Franz M, Hornsby G, Kriska A, Marrero D, Ullrich I, Verity LS (2000) American College of Sports Medicine position stand. Exercise and type 2 diabetes. Med Sci Sports Exerc 32:1345–1360

    Article  PubMed  CAS  Google Scholar 

  • Assmann G, Gotto AM Jr (2004) HDL cholesterol and protective factors in atherosclerosis. Circulation 109:III8–III14

    Article  PubMed  Google Scholar 

  • Benton CR, Nickerson JG, Lally J, Han XX, Holloway GP, Glatz JF, Luiken JJ, Graham TE, Heikkila JJ, Bonen A (2008) Modest PGC-1alpha overexpression in muscle in vivo is sufficient to increase insulin sensitivity and palmitate oxidation in subsarcolemmal, not intermyofibrillar, mitochondria. J Biol Chem 283:4228–4240

    Article  PubMed  CAS  Google Scholar 

  • Bombardelli E, Morazzoni P (1995) Vitis vinifera L. Fitoterapia 66:291–317

    CAS  Google Scholar 

  • Bonen A, Dohm GL, van Loon LJ (2006) Lipid metabolism, exercise and insulin action. Essays Biochem 42:47–59

    Article  PubMed  CAS  Google Scholar 

  • Bruce CR, Thrush AB, Mertz VA, Bezaire V, Chabowski A, Heigenhauser GJ, Dyck DJ (2006) Endurance training in obese humans improves glucose tolerance and mitochondrial fatty acid oxidation and alters muscle lipid content. Am J Physiol Endocrinol Metab 291:E99–E107

    Article  PubMed  CAS  Google Scholar 

  • Calvo JA, Daniels TG, Wang X, Paul A, Lin J, Spiegelman BM, Stevenson SC, Rangwala SM (2008) Muscle-specific expression of PPAR gamma coactivator-1alpha improves exercise performance and increases peak oxygen uptake. J Appl Physiol 104:1304–1312

    Article  PubMed  CAS  Google Scholar 

  • Davies KJ, Packer L, Brooks GA (1981) Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training. Arch Biochem Biophys 209:539–554

    Article  PubMed  CAS  Google Scholar 

  • Fritz IB, Yue KT (1963) Long-chain carnitine acyltransferase and the role of acylcarnitine derivatives in the catalytic increase of fatty acid oxidation induced by carnitine. J Lipid Res 4:279–288

    PubMed  CAS  Google Scholar 

  • Gordon DJ, Rifkind BM (1989) High-density lipoprotein: the clinical implications of recent studies. N Engl J Med 321:1311–1316

    Article  PubMed  CAS  Google Scholar 

  • Handschin C, Chin S, Li P, Liu F, Maratos-Flier E, Lebrasseur NK, Yan Z, Spiegelman BM (2007) Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals. J Biol Chem 282:30014–30021

    Article  PubMed  CAS  Google Scholar 

  • Hawley JA, Brouns F, Jeukendrup A (1998) Strategies to enhance fat utilisation during exercise. Sports Med 25:241–257

    Article  PubMed  CAS  Google Scholar 

  • Holloszy JO, Kohrt WM, Hansen PA (1998) The regulation of carbohydrate and fat metabolism during and after exercise. Front Biosci 3:D1011–D1027

    PubMed  CAS  Google Scholar 

  • Horowitz JF (2003) Fatty acid mobilization from adipose tissue during exercise. Trends Endocrinol Metab 14:386–392

    Article  PubMed  CAS  Google Scholar 

  • Howlett RA, Heigenhauser GJ, Hultman E, Hollidge-Horvat MG, Spriet LL (1999) Effects of dichloroacetate infusion on human skeletal muscle metabolism at the onset of exercise. Am J Physiol 277:E18–E25

    PubMed  CAS  Google Scholar 

  • Hunter GR, Larson-Meyer DE, Sirikul B, Newcomer BR (2006) Muscle metabolic function and free-living physical activity. J Appl Physiol 101:1356–1361

    Article  PubMed  CAS  Google Scholar 

  • Ivy JL (1999) Role of carbohydrate in physical activity. Clin Sports Med 18:469–484

    Article  PubMed  CAS  Google Scholar 

  • Jeukendrup AE, Saris WH, Wagenmakers AJ (1998) Fat metabolism during exercise: a review—part III: effects of nutritional interventions. Int J Sports Med 19:371–379

    Article  PubMed  CAS  Google Scholar 

  • Kamijo T, Aoyama T, Miyazaki J, Hashimoto T (1993) Molecular cloning of the cDNAs for the subunits of rat mitochondrial fatty acid beta-oxidation multienzyme complex. Structural and functional relationships to other mitochondrial and peroxisomal beta-oxidation enzymes. J Biol Chem 268:26452–26460

    PubMed  CAS  Google Scholar 

  • Kiesewetter H, Koscielny J, Kalus U, Vix JM, Peil H, Petrini O, van Toor BS, de Mey C (2000) Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II). A randomized, double-blind, placebo-controlled trial. Arzneimittelforschung 50:109–117

    PubMed  CAS  Google Scholar 

  • Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122

    Article  PubMed  CAS  Google Scholar 

  • MacRae HS, Mefferd KM (2006) Dietary antioxidant supplementation combined with quercetin improves cycling time trial performance. Int J Sport Nutr Exerc Metab 16:405–419

    PubMed  CAS  Google Scholar 

  • Matsumoto K, Ishihara K, Tanaka K, Inoue K, Fushiki T (1996) An adjustable-current swimming pool for the evaluation of endurance capacity of mice. J Appl Physiol 81:1843–1849

    PubMed  CAS  Google Scholar 

  • Monagas M, Hernández-Ledesma B, Gómez-Cordovés C, Bartolomé B (2006) Commercial dietary ingredients from Vitis vinifera L. leaves and grape skins: antioxidant and chemical characterization. J Agric Food Chem 54:319–327

    Article  PubMed  CAS  Google Scholar 

  • Murase T, Haramizu S, Shimotoyodome A, Nagasawa A, Tokimitsu I (2005) Green tea extract improves endurance capacity and increases muscle lipid oxidation in mice. Am J Physiol Regul Integr Comp Physiol 288:R708–R715

    Article  PubMed  CAS  Google Scholar 

  • Murase T, Haramizu S, Shimotoyodome A, Tokimitsu I, Hase T (2006) Green tea extract improves running endurance in mice by stimulating lipid utilization during exercise. Am J Physiol Regul Integr Comp Physiol 290:R1550–R1556

    Article  PubMed  CAS  Google Scholar 

  • Ryu S, Choi SK, Joung SS, Suh H, Cha YS, Lee S, Lim K (2001) Caffeine as a lipolytic food component increases endurance performance in rats and athletes. J Nutr Sci Vitaminol (Tokyo) 47:139–146

    CAS  Google Scholar 

  • Schaefer E, Peil H, Ambrosetti L, Petrini O (2003) Oedema protective properties of the red vine leaf extract AS 195 (Folia vitis viniferae) in the treatment of chronic venous insufficiency. A 6-week observational clinical trial. Arzneimittelforschung 53:243–246

    PubMed  CAS  Google Scholar 

  • Sugden MC, Bulmer K, Gibbons GF, Holness MJ (2001) Role of peroxisome proliferator-activated receptor-alpha in the mechanism underlying changes in renal pyruvate dehydrogenase kinase isoform 4 protein expression in starvation and after refeeding. Arch Biochem Biophys 395:246–252

    Article  PubMed  CAS  Google Scholar 

  • Tsuda T, Ueno Y, Kojo H, Yoshikawa T, Osawa T (2005) Gene expression profile of isolated rat adipocytes treated with anthocyanins. Biochim Biophys Acta 1733:137–147

    PubMed  CAS  Google Scholar 

  • Van Harmelen V, Lönnqvist F, Thörne A, Wennlund A, Large V, Reynisdottir S, Arner P (1997) Noradrenaline-induced lipolysis in isolated mesenteric, omental and subcutaneous adipocytes from obese subjects. Int J Obes Relat Metab Disord 21:972–979

    Article  PubMed  Google Scholar 

  • Vega RB, Huss JM, Kelly DP (2000) The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 20:1868–1876

    Article  PubMed  CAS  Google Scholar 

  • Wolfe RR, Klein S, Carraro F, Weber JM (1990) Role of triglyceride-fatty acid cycle in controlling fat metabolism in humans during and after exercise. Am J Physiol 258:E382–E389

    PubMed  CAS  Google Scholar 

  • Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Takatoshi Murase.

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Communicated by Susan A. Ward.

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Minegishi, Y., Haramizu, S., Hase, T. et al. Red grape leaf extract improves endurance capacity by facilitating fatty acid utilization in skeletal muscle in mice. Eur J Appl Physiol 111, 1983–1989 (2011). https://doi.org/10.1007/s00421-011-1826-2

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  • DOI: https://doi.org/10.1007/s00421-011-1826-2

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