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Fructose Metabolism and Exercise: Physiological Applications and Limitations Unicentre CH-1015 Lausanne http://serval.unil.ch RRRYear : 2017 Fructose Metabolism and Exercise: Physiological Applications and Limitations Rosset Robin Rosset Robin, 2017, Fructose Metabolism and Exercise: Physiological Applications and Limitations Originally published at : Thesis, University of Lausanne Posted at the University of Lausanne Open Archive http://serval.unil.ch Document URN : urn:nbn:ch:serval-BIB_0B79F131EB906 Droits d’auteur L'Université de Lausanne attire expressément l'attention des utilisateurs sur le fait que tous les documents publiés dans l'Archive SERVAL sont protégés par le droit d'auteur, conformément à la loi fédérale sur le droit d'auteur et les droits voisins (LDA). A ce titre, il est indispensable d'obtenir le consentement préalable de l'auteur et/ou de l’éditeur avant toute utilisation d'une oeuvre ou d'une partie d'une oeuvre ne relevant pas d'une utilisation à des fins personnelles au sens de la LDA (art. 19, al. 1 lettre a). A défaut, tout contrevenant s'expose aux sanctions prévues par cette loi. Nous déclinons toute responsabilité en la matière. Copyright The University of Lausanne expressly draws the attention of users to the fact that all documents published in the SERVAL Archive are protected by copyright in accordance with federal law on copyright and similar rights (LDA). Accordingly it is indispensable to obtain prior consent from the author and/or publisher before any use of a work or part of a work for purposes other than personal use within the meaning of LDA (art. 19, para. 1 letter a). Failure to do so will expose offenders to the sanctions laid down by this law. We accept no liability in this respect. Département de Physiologie Fructose Metabolism and Exercise: Physiological Applications and Limitations Thèse de doctorat ès sciences de la vie (PhD) Présentée à la faculté de Biologie et de Médecine de l’Université de Lausanne par Robin Rosset Titulaire d’une Maîtrise Universitaire en Biologie Médicale de l’Université de Lausanne Jury Prof. Michel Duchosal, Président du Jury Prof. Luc Tappy, Directeur de Thèse Dr. Gérald Gremion, Expert Dr. Hervé Dubouchaud, Expert Lausanne 2017 Unicentre CH-1015 Lausanne http://serval.unil.ch 2017 Fructose Metabolism and Exercise: Physiological Applications and Limitations Robin Rosset Robin Rosset, 2017, Fructose Metabolism and Exercise: Physiological Applications and Limitations Originally published at: Thesis, University of Lausanne Posted at the University of Lausanne Open Archive http://serval.unil.ch Document URN: Droits d’auteur L'Université de Lausanne attire expressément l'attention des utilisateurs sur le fait que tous les documents publiés dans l'Archive SERVAL sont protégés par le droit d'auteur, conformément à la loi fédérale sur le droit d'auteur et les droits voisins (LDA). A ce titre, il est indispensable d'obtenir le consentement préalable de l'auteur et/ou de l’éditeur avant toute utilisation d'une œuvre ou d'une partie d'une œuvre ne relevant pas d'une utilisation à des fins personnelles au sens de la LDA (art. 19, al. 1 lettre a). A défaut, tout contrevenant s'expose aux sanctions prévues par cette loi. Nous déclinons toute responsabilité en la matière. Copyright The University of Lausanne expressly draws the attention of users to the fact that all documents published in the SERVAL Archive are protected by copyright in accordance with federal law on copyright and similar rights (LDA). Accordingly it is indispensable to obtain prior consent from the author and/or publisher before any use of a work or part of a work for purposes other than personal use within the meaning of LDA (art. 19, para. 1 letter a). Failure to do so will expose offenders to the sanctions laid down by this law. We accept no liability in this respect. Contents I. Summary iii II. Résumé iv III. Remerciements v IV. Abbreviations vi Introduction V. Fructose Metabolism: A Natural Sugar with Specific Effects a. A general perspective 1 b. Overview of fructose metabolism 2 c. Overview of the metabolic effects of fructose 10 VI. Exercise Physiology: Integrated Muscle Energetics a. Overview of skeletal muscle energetics 13 b. Muscle as part of energy systems 20 c. Muscle energy stores 23 VII. Sports Nutrition: Is there a Role for fructose? Fructose Metabolism: Is there a Role for Exercise? a. Overview of fructose uses in sports nutrition 25 b. Exercise protection against fructose metabolic effects 29 VIII. Manuscript 1: Abstract 31 IX. Manuscript 2: Abstract 32 i Aims and Hypothesis X. Working Hypothesis: Delineating the Fructose-Exercise Relationship 33 Experimental Results XI. Manuscript 3: Main Results 34 XII. Manuscript 4: Main Results 36 XIII. Manuscript 5: Main Results 38 Discussion XIV. General Discussion: Fructose Metabolism in an Exercise Context a. An integrative model of fructose metabolism 40 b. Practical implications 46 c. Conclusions 47 XV. Manuscript 6: Abstract 49 Annexes XVI. References 50 XVII. List of Publications 60 Manuscript 1 62 Manuscript 2 71 Manuscript 3 82 Manuscript 4 91 Manuscript 5 101 Manuscript 6 116 ii I. Summary Fructose has gained renewed interest for its suspected role in cardiometabolic diseases and as a performance enhancer in sports nutrition. Both are related to fructose metabolism in the liver resulting in no plasma glucose or insulin peaks, but causing postprandial hyperlactatemia and hypertriglyceridemia. The general aim of this work was to further investigate fructose metabolism and to find potential new applications of fructose that may improve performance. In a first experimental study, we evaluated how fructose metabolism is modulated by an exercise session performed before or after fructose ingestion. Although confirming that fructose is extensively oxidized during exercise, our results also showed that fructose metabolism was largely unaltered when ingested during recovery. In a second study, we used fructose in mixed-meals provided for 24 h postexercise to specifically favor muscle energy storage and subsequent exercise performance. Compared to an isocaloric control, fructose did however not further improve muscle recovery, and fructose impaired whole-body glycogen storage and subsequent exercise performance. In a third study, we investigated the effects of glucose-fructose ingestion during training sessions on lactate metabolism, at rest and during exercise, pre-training and post-training. Interestingly, training with glucose- fructose increased lactate production, consumption and oxidation at rest but not during exercise, and an important part of lactate was directed to non-oxidative fates in all conditions. Altogether, the present results indicate an ambivalent role of fructose, efficient to fuel muscle work, but inefficient during postexercise recovery. This may be largely due to fructose conversion into lactate, furnishing an alternative fuel during exercise that however needs to be stored for an extra energy cost in resting times. In turn, this “reverse Cori cycle” may represent an important mechanism by which fructose effects are matched to physical activity. iii Résumé Le fructose est suspecté de jouer un rôle dans les maladies cardio-métaboliques, et est largement utilisé en nutrition du sport. Ceci est lié à son métabolisme hépatique, entraînant l’absence de pics glycémiques et insulinémiques, mais causant une hyperlactatémie et hypertriglycéridémie postprandiale. Le but général de ce travail était de mieux comprendre le métabolisme du fructose et de l’utiliser afin d’améliorer la performance d’exercice physique. Dans une première étude, nous avons évalué comment le métabolisme du fructose peut être modulé par un exercice effectué avant ou après ingestion. Tout en confirmant que le fructose est bien oxydé à l’exercice, nos résultats ont aussi montré que son métabolisme n’est pas modifié en récupération. La deuxième étude visait à utiliser des repas mixtes contenant fructose, graisse et protéines et ingérés pendant 24 h, afin d’améliorer la récupération des stocks énergétiques et la future performance. En comparaison avec un contrôle, le fructose n’a pas amélioré la récupération musculaire, a limité le stockage glycogénique total et a diminué la performance. Dans une troisième étude, nous avons étudié l’effet de l’ingestion de glucose-fructose durant l’entraînement sur le métabolisme du lactate, au repos et à l’exercice, avant et après entraînement. S’entraîner avec du glucose-fructose a augmenté la production, la consommation et l’oxydation de lactate plasmatique au repos mais pas à l’exercice, tandis qu’une part importante de ce lactate était dirigée vers des devenirs non-oxydatifs. En résumé, nos résultats indiquent un rôle ambivalent du fructose, efficace pour nourrir le muscle à l’exercice, mais inefficace en récupération. Ceci pourrait être largement dû à la circulation du fructose en lactate, donnant un carburant alternatif à l’exercice qui cependant coûte de l’énergie lors de son restockage au repos. Ce « cycle de Cori inversé » pourrait être un important mécanisme par lequel les effets du fructose sont reliés à l’activité physique. iv II. Remerciements Ces années au Département de Physiologie ont été faites de hauts et de bas, et c’est grâce à un certain nombre de personnes que j’ai pu réaliser ce travail. Ainsi, je voudrais remercier les membres de mon jury pour leur bienveillance, et tout particulièrement Luc, à qui j’exprime ma profonde gratitude pour m’avoir permis de me former dans un domaine qui me passionne. Merci pour ta patience, ta confiance et la liberté laissée. J’ai beaucoup appris à tes côtés durant ces années, qui m’ont apporté une expérience sans égale. Un vibrant hommage aussi à Philippe, pour tes qualités humaines et la rigueur que tu inspires, ainsi que pour m’avoir ouvert les portes du Département de Physiologie. Je souhaite aussi mentionner Virgile, pour ton partage de connaissances (sur et à côté du vélo), tes coups de sang (justifiés) et ton soutien durant toute la première partie de mon travail.
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