Deep phenotyping of patients with MASLD upon high-intensity interval training
Veera Houttu1,2,3,4, Ulrika Boulund1,2,3,4, Marian Troelstra5
1Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
JHEP Reports : Innovation in Hepatology
|March 7, 2025
Summary
High-intensity interval training (HIIT) improved cardiorespiratory fitness in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, HIIT did not lead to histological improvements in MASLD, suggesting longer trials are needed.
Area of Science:
- Hepatology
- Exercise Physiology
- Metabolic Diseases
Background:
- Exercise is crucial for managing metabolic dysfunction-associated steatotic liver disease (MASLD).
- Mechanisms and therapeutic effects of exercise on active MASLD (MASH) remain unclear.
- Multi-omic phenotyping was used to investigate exercise effects in MASLD-MASH patients.
Purpose of the Study:
- To evaluate the therapeutic effect of high-intensity interval training (HIIT) on MASLD.
- To characterize the underlying mechanisms of exercise intervention in MASLD-MASH.
- To assess changes in cardiorespiratory fitness and liver health markers.
Main Methods:
- 15 MASLD patients underwent 12 weeks of HIIT and home-based training.
- Evaluations included histology, transient elastography, and MRI for MASLD.
- Multi-omic analyses (RNA sequencing, metagenomics, metabolomics) were performed on various tissues and biofluids.
Main Results:
- HIIT significantly increased VO2max, indicating improved cardiorespiratory fitness.
- No histological improvements in steatosis, MASH, or fibrosis were observed.
- HIIT induced beneficial gene expression changes in adipose tissue and liver, and altered gut microbiota and metabolites.
Conclusions:
- HIIT enhances cardiorespiratory fitness and induces favorable molecular changes in MASLD patients.
- Exercise intervention did not translate to histological liver improvement in this trial.
- Further research with longer exercise interventions is necessary to confirm exercise's role in MASLD treatment.


