BACKGROUND: Exercise has profound pleiotropic health benefits, yet the underlying mechanisms remain incompletely understood. Endocrine FGF21, bile acids (BAs), and BA-induced FGF19 have emerged as metabolic signaling molecules. Here, we investigated if dissimilar modes of exercise, resistance exercise (RE) and endurance exercise (EE), regulate plasma BAs, FGF19, and FGF21 in humans. METHODS:Ten healthy, moderately trained males were enrolled in a randomized crossover study of 1 hour of bicycling at 70% of VO2peak (EE) and 1 hour of high-volume RE. Hormones and metabolites were measured in venous blood and sampled before and after exercise and at 15, 30, 60, 90, 120, and 180 minutes after exercise. RESULTS: We observed exercise mode-specific changes in plasma concentrations of FGF19 and FGF21. Whereas FGF19 decreased following RE (P < 0.001), FGF21 increased in response to EE (P < 0.001). Total plasma BAs decreased exclusively following RE (P < 0.05), but the composition of BAs changed in response to both types of exercise. Notably, circulating levels of the potent TGR5 receptor agonist, lithocholic acid, increased with both types of exercise (P < 0.001). CONCLUSION: This study reveals divergent effects of EE and RE on circulating concentrations of the BA species, FGF19, and FGF21. We identify temporal relationships between decreased BA and FGF19 following RE and a sharp disparity in FGF21 concentrations, with EE eliciting a clear increase parallel to that of glucagon. FUNDING: The Novo Nordisk Foundation (NNF17OC0026114) and the Lundbeck Foundation (R238-2016-2859).
RCT Entities:
BACKGROUND: Exercise has profound pleiotropic health benefits, yet the underlying mechanisms remain incompletely understood. Endocrine FGF21, bile acids (BAs), and BA-induced FGF19 have emerged as metabolic signaling molecules. Here, we investigated if dissimilar modes of exercise, resistance exercise (RE) and endurance exercise (EE), regulate plasma BAs, FGF19, and FGF21 in humans. METHODS: Ten healthy, moderately trained males were enrolled in a randomized crossover study of 1 hour of bicycling at 70% of VO2peak (EE) and 1 hour of high-volume RE. Hormones and metabolites were measured in venous blood and sampled before and after exercise and at 15, 30, 60, 90, 120, and 180 minutes after exercise. RESULTS: We observed exercise mode-specific changes in plasma concentrations of FGF19 and FGF21. Whereas FGF19 decreased following RE (P < 0.001), FGF21 increased in response to EE (P < 0.001). Total plasma BAs decreased exclusively following RE (P < 0.05), but the composition of BAs changed in response to both types of exercise. Notably, circulating levels of the potent TGR5 receptor agonist, lithocholic acid, increased with both types of exercise (P < 0.001). CONCLUSION: This study reveals divergent effects of EE and RE on circulating concentrations of the BA species, FGF19, and FGF21. We identify temporal relationships between decreased BA and FGF19 following RE and a sharp disparity in FGF21 concentrations, with EE eliciting a clear increase parallel to that of glucagon. FUNDING: The Novo Nordisk Foundation (NNF17OC0026114) and the Lundbeck Foundation (R238-2016-2859).
Authors: Evie P M Broeders; Emmani B M Nascimento; Bas Havekes; Boudewijn Brans; Kay H M Roumans; Anne Tailleux; Gert Schaart; Mostafa Kouach; Julie Charton; Benoit Deprez; Nicole D Bouvy; Felix Mottaghy; Bart Staels; Wouter D van Marken Lichtenbelt; Patrick Schrauwen Journal: Cell Metab Date: 2015-07-30 Impact factor: 27.287
Authors: Gregory J Morton; Miles E Matsen; Deanna P Bracy; Thomas H Meek; Hong T Nguyen; Darko Stefanovski; Richard N Bergman; David H Wasserman; Michael W Schwartz Journal: J Clin Invest Date: 2013-11 Impact factor: 14.808
Authors: Kirk M Habegger; Kerstin Stemmer; Christine Cheng; Timo D Müller; Kristy M Heppner; Nickki Ottaway; Jenna Holland; Jazzminn L Hembree; David Smiley; Vasily Gelfanov; Radha Krishna; Ayman M Arafat; Anish Konkar; Sara Belli; Martin Kapps; Stephen C Woods; Susanna M Hofmann; David D'Alessio; Paul T Pfluger; Diego Perez-Tilve; Randy J Seeley; Morichika Konishi; Nobuyujki Itoh; Alexei Kharitonenkov; Joachim Spranger; Richard D DiMarchi; Matthias H Tschöp Journal: Diabetes Date: 2013-01-10 Impact factor: 9.461
Authors: Trisha J Grevengoed; Samuel Aj Trammell; Jens S Svenningsen; Mikhail V Makarov; Thomas Svava Nielsen; Jens Christian Brings Jacobsen; Jonas T Treebak; Philip C Calder; Marie E Migaud; Benjamin F Cravatt; Matthew P Gillum Journal: J Clin Invest Date: 2021-03-15 Impact factor: 14.808
Authors: Adrianna Maurer; Jaimie L Ward; Kelsey Dean; Sandra A Billinger; Haixia Lin; Kelly E Mercer; Sean H Adams; John P Thyfault Journal: J Appl Physiol (1985) Date: 2020-08-27
Authors: Alana E O'Mara; James W Johnson; Joyce D Linderman; Robert J Brychta; Suzanne McGehee; Laura A Fletcher; Yael A Fink; Devika Kapuria; Thomas M Cassimatis; Nathan Kelsey; Cheryl Cero; Zahraa Abdul Sater; Francesca Piccinini; Alison S Baskin; Brooks P Leitner; Hongyi Cai; Corina M Millo; William Dieckmann; Mary Walter; Norman B Javitt; Yaron Rotman; Peter J Walter; Marilyn Ader; Richard N Bergman; Peter Herscovitch; Kong Y Chen; Aaron M Cypess Journal: J Clin Invest Date: 2020-05-01 Impact factor: 14.808
Authors: Tracey G Simon; Mi Na Kim; Xiao Luo; Wanshui Yang; Yanan Ma; Dawn Q Chong; Charles S Fuchs; Jeffrey A Meyerhardt; Kathleen E Corey; Raymond T Chung; Meir Stampfer; Xuehong Zhang; Edward L Giovannucci; Andrew T Chan Journal: J Hepatol Date: 2020-01-15 Impact factor: 25.083
Authors: Stephanie Holm; Anna S Husted; Louise J Skov; Thomas H Morville; Christoffer A Hagemann; Tina Jorsal; Morten Dall; Alexander Jakobsen; Anders B Klein; Jonas T Treebak; Filip K Knop; Thue W Schwartz; Christoffer Clemmensen; Birgitte Holst Journal: Endocrinology Date: 2022-06-01 Impact factor: 5.051
Authors: Ambrin Farizah Babu; Susanne Csader; Ville Männistö; Milla-Maria Tauriainen; Heikki Pentikäinen; Kai Savonen; Anton Klåvus; Ville Koistinen; Kati Hanhineva; Ursula Schwab Journal: Sci Rep Date: 2022-04-20 Impact factor: 4.996
Authors: Samuel A J Trammell; Jens S Svenningsen; Jens J Holst; Matthew P Gillum; Rune E Kuhre Journal: Molecules Date: 2020-05-20 Impact factor: 4.411
Authors: Matthew Nayor; Ravi V Shah; Patricia E Miller; Jasmine B Blodgett; Melissa Tanguay; Alexander R Pico; Venkatesh L Murthy; Rajeev Malhotra; Nicholas E Houstis; Amy Deik; Kerry A Pierce; Kevin Bullock; Lucas Dailey; Raghava S Velagaleti; Stephanie A Moore; Jennifer E Ho; Aaron L Baggish; Clary B Clish; Martin G Larson; Ramachandran S Vasan; Gregory D Lewis Journal: Circulation Date: 2020-09-15 Impact factor: 29.690