Effects of High-Intensity Interval Training and Moderate-Intensity Continuous Training on PGC-1α, SIRT3, and Non-Alcoholic Fatty Liver Disease: A Narrative Review
Abstract
Background & Objectives: This narrative review examines the effects of high-intensityinterval training (HIIT) and moderate-intensity continuous training (MICT) on keymitochondrial biomarkers, namely peroxisome proliferator-activated receptor gammacoactivator 1-alpha (PGC-1α) and sirtuin 3 (SIRT3), and evaluates their therapeutic rolesin metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known asnon-alcoholic fatty liver disease (NAFLD).
Materials & Methods: A systematic literature search was conducted in the Scopus,PubMed, ScienceDirect, and Elsevier databases using the keywords “HIIT,” “MICT,”“PGC-1α,” “SIRT3,” and “MASLD,” with no temporal restrictions applied. Studiespublished up to October 2025 were included. The initial search yielded approximately 600articles; following duplicate removal and title and abstract screening, 83 relevant studieswere selected for inclusion. Priority was given to recent evidence published between 2022and 2025 that incorporated the updated MASLD nomenclature.
Results: Both HIIT and MICT significantly upregulate PGC-1α and SIRT3 expression,thereby enhancing mitochondrial biogenesis, reducing oxidative stress, and improvinghepatic lipid metabolism. These molecular adaptations are associated with clinicallymeaningful outcomes, including reduced hepatic fat accumulation, improved insulinsensitivity, and enhanced liver function. HIIT tends to elicit more rapid molecular andmetabolic adaptations, whereas MICT is more consistently associated with sustainedlong-term benefits.
Conclusion: HIIT and MICT represent effective, evidence-based exercise interventionsfor the management of MASLD through modulation of mitochondrial signaling pathways.HIIT may be preferable when time efficiency is a priority, whereas MICT may be moresuitable for long-term adherence. An individualized exercise prescription, beginning withMICT and progressively incorporating HIIT, is recommended. The primary limitationsof this review include its narrative design and the potential for publication bias; therefore,future large-scale randomized controlled trials across diverse populations are warranted.