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JCI Insight. 2018 Aug 9;3(15). pii: 122737. doi: 10.1172/jci.insight.122737. eCollection 2018 Aug 9.

Divergent effects of resistance and endurance exercise on plasma bile acids, FGF19, and FGF21 in humans.

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Xlab, Center for Healthy Aging, Department of Biomedical Sciences, and.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.



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.


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.


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).


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.


The Novo Nordisk Foundation (NNF17OC0026114) and the Lundbeck Foundation (R238-2016-2859).


Endocrinology; Glucose metabolism; Metabolism; Skeletal muscle

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