Effect of exercise intensity on circulating hepatokine concentrations in healthy men

Scott A. Willis, Jack A. Sargeant, Alice E. Thackray, Thomas Yates, David J. Stensel, Guruprasad P. Aithal, James A. King*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Fibroblast growth factor 21 (FGF21), follistatin and leukocyte cell-derived chemotaxin 2 (LECT2) are novel hepatokines that are modulated by metabolic stresses. This study investigated whether exercise intensity modulates the hepatokine response to acute exercise. Ten young, healthy men undertook three 8-h experimental trials: moderate-intensity exercise (MOD; 55% peak oxygen uptake), high-intensity exercise (HIGH; 75% peak oxygen uptake), and control (CON; rest), in a randomised, counterbalanced order. Exercise trials commenced with a treadmill run of varied duration to match gross exercise energy expenditure between trials (MOD vs HIGH; 2475 ± 70 vs 2488 ± 58 kJ). Circulating FGF21, follistatin, LECT2, glucagon, insulin, glucose and nonesterified fatty acids (NEFA) were measured before exercise and at 0, 1, 2, 4, and 7 h postexercise. Plasma FGF21 concentrations were increased up to 4 h postexercise compared with CON (P ≤ 0.022) with greater increases observed at 1, 2, and 4 h postexercise during HIGH versus MOD (P ≤ 0.025). Irrespective of intensity (P ≥ 0.606), plasma follistatin concentrations were elevated at 4 and 7 h postexercise (P ≤ 0.053). Plasma LECT2 concentrations were increased immediately postexercise (P ≤ 0.046) but were not significant after correcting for plasma volume shifts. Plasma glucagon (1 h; P = 0.032) and NEFA (4 and 7 h; P ≤ 0.029) responses to exercise were accentuated in HIGH versus MOD. These findings demonstrate that acute exercise augments circulating FGF21 and follistatin. Exercise-induced changes in FGF21 are intensity-dependent and may support the greater metabolic benefit of high-intensity exercise.

Original languageEnglish
Pages (from-to)1065-1072
Number of pages8
JournalApplied Physiology, Nutrition and Metabolism
Issue number10
Publication statusPublished - 2019
Externally publishedYes


  • Exercise
  • FGF21
  • Follistatin
  • Hepatokines
  • Insulin resistance
  • LECT2
  • Liver
  • Physical activity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)


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