Summary:
In obese adult men (n=44) randomly assigned to exercise or control groups, 12-week supervised interventions of continuous aerobic training, Tabata, or high-intensity interval training (HIIT) performed 3 sessions per week for 60 minutes significantly reduced weight, BMI, body fat percentage, and circulating hepatokine levels including fetuin-B, FGF-21, FGL-1, and selenoprotein P compared to a non-exercising control group, though it was associated with no reported adverse effects, with Tabata and HIIT showing the most pronounced hepatokine modulation.
| PICO | Description |
|---|---|
| Population | 44 obese adult men randomly assigned to four groups: control, endurance training (ET), Tabata, and high-intensity interval training (HIIT). |
| Intervention | 12 weeks of supervised physical activity (3 sessions per week, 60 minutes per session) involving either continuous aerobic (endurance) training, Tabata protocol, or high-intensity interval training. |
| Comparison | Non-exercising control group maintaining usual lifestyle without structured exercise intervention. |
| Outcome | Significant reductions in fetuin-B (HIIT: -0.13; Tabata: -0.14 vs control), FGF-21 (ET: -19.1; HIIT: -26.22; Tabata: -22.8 vs control), FGL-1 (ET: -11.5; HIIT: -8.1; Tabata: -11.3), selenoprotein P, BMI, body fat percentage, and weight. Tabata and HIIT showed most pronounced effects. No adverse effects reported. |
Clinical Context
Hepatokines—proteins secreted by the liver that act on distant tissues—have emerged as important mediators linking hepatic metabolism to systemic metabolic health. In obesity and non-alcoholic fatty liver disease (NAFLD), hepatokine dysregulation contributes to insulin resistance, dyslipidemia, and cardiovascular risk. Key hepatokines including fetuin-B, fibroblast growth factor 21 (FGF-21), fibrinogen-like protein 1 (FGL-1), and selenoprotein P are elevated in obesity and correlate with metabolic dysfunction.
Exercise improves metabolic health through multiple mechanisms, but the effects on hepatokine secretion are less well characterized than traditional metabolic markers. Understanding how different exercise modalities affect hepatokine profiles could inform precision exercise prescription for metabolic disease. While continuous moderate-intensity aerobic exercise has established metabolic benefits, high-intensity interval training (HIIT) and ultra-high-intensity Tabata protocols have gained attention for their time-efficiency and potentially superior metabolic adaptations.
This study directly compared three exercise modalities—continuous endurance training, Tabata, and HIIT—for their effects on circulating hepatokines in obese men. The findings provide mechanistic insights into how different exercise intensities modulate liver-derived metabolic signaling molecules and may help optimize exercise recommendations for individuals with obesity-related metabolic dysfunction.
Clinical Pearls
1. All Exercise Modalities Improve Hepatokine Profiles: Continuous endurance training, Tabata, and HIIT all significantly reduced circulating levels of fetuin-B, FGF-21, FGL-1, and selenoprotein P compared to sedentary controls. This indicates that the metabolic benefits of exercise extend to hepatokine modulation regardless of specific protocol, though magnitude differs by modality.
2. High-Intensity Protocols Show Enhanced Effects: Tabata and HIIT produced the most pronounced hepatokine reductions, suggesting that exercise intensity may be a key determinant of liver-derived metabolic signaling. These time-efficient protocols may offer superior hepatokine modulation compared to traditional moderate-intensity continuous exercise.
3. Hepatokine Changes Parallel Body Composition Improvements: The reductions in hepatokines occurred alongside decreases in BMI, body fat percentage, and weight. While causality cannot be established, this association suggests hepatokine improvement may be partially mediated by fat mass reduction and partially by exercise-induced hepatic adaptations.
4. Safety Profile Supports High-Intensity Exercise in Obesity: No adverse effects were reported across any exercise group, including the high-intensity Tabata and HIIT protocols. This supports the safety of supervised high-intensity exercise in obese individuals, though appropriate screening and progression remain important.
Practical Application
For obese patients seeking metabolic improvement, consider high-intensity interval training or Tabata protocols as time-efficient alternatives to traditional continuous aerobic exercise. The superior hepatokine modulation with these modalities may translate to enhanced metabolic benefits, particularly for patients with limited exercise time availability. Supervise initial sessions and ensure appropriate cardiovascular screening before high-intensity exercise.
Recognize that all exercise modalities produced significant benefits—the best exercise is the one patients will consistently perform. For individuals who prefer or better tolerate moderate-intensity continuous exercise, this remains an effective option for hepatokine improvement. Match exercise prescription to patient preference, fitness level, and comorbidities.
Consider hepatokine measurement (particularly FGF-21 and fetuin-B where available) as emerging biomarkers of metabolic response to exercise interventions, though these are not yet standard clinical tests. Changes in traditional markers (weight, body composition, liver enzymes, lipids) remain the practical monitoring approach.
Broader Evidence Context
This study adds to growing literature on hepatokines as mediators of exercise-induced metabolic improvement. Previous studies have shown that aerobic exercise reduces hepatokine levels, but direct comparisons between exercise modalities are limited. The finding that HIIT and Tabata may produce enhanced hepatokine modulation aligns with other studies showing superior metabolic adaptations to high-intensity exercise.
Hepatokine research is evolving rapidly, with ongoing investigation into their roles as therapeutic targets and biomarkers. FGF-21 analogs are in clinical development for metabolic disease, making understanding of exercise effects on this pathway clinically relevant.
Study Limitations
Small sample size (n=44) limits statistical power for between-group comparisons. Male-only population restricts generalizability to women. The 12-week duration may not capture long-term effects or maintenance of hepatokine changes. Hepatokine levels were not correlated with hepatic fat content or liver histology. Dietary intake was not controlled, introducing potential confounding.
Bottom Line
All exercise modalities reduce circulating hepatokines in obese men, with high-intensity protocols (Tabata and HIIT) showing the most pronounced effects on fetuin-B, FGF-21, FGL-1, and selenoprotein P, supporting high-intensity exercise as an effective and time-efficient approach for modulating liver-derived metabolic signaling.
Source: Ataeinosrat, Ali, et al. “Hepatokines Modulation in Obesity: Which Exercise Training Model Is Better in Men with Obesity?” Frontiers in Endocrinology. Read article
