Effects of High-Intensity Interval Training and Moderate-Intensity Continuous Training on PGC-1α, SIRT3, and Non-Alcoholic Fatty Liver Disease: A Narrative Review

Background & Objectives: This narrative review examines the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on key mitochondrial biomarkers, namely peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and sirtuin 3 (SIRT3), and evaluates their therapeutic roles in metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-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. Studies published up to October 2025 were included. The initial search yielded approximately 600 articles; following duplicate removal and title and abstract screening, 83 relevant studies were selected for inclusion. Priority was given to recent evidence published between 2022 and 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 improving hepatic lipid metabolism. These molecular adaptations are associated with clinically meaningful outcomes, including reduced hepatic fat accumulation, improved insulin sensitivity, and enhanced liver function. HIIT tends to elicit more rapid molecular and metabolic adaptations, whereas MICT is more consistently associated with sustained long-term benefits. Conclusion: HIIT and MICT represent effective, evidence-based exercise interventions for the management of MASLD through modulation of mitochondrial signaling pathways. HIIT may be preferable when time efficiency is a priority, whereas MICT may be more suitable for long-term adherence. An individualized exercise prescription, beginning with MICT and progressively incorporating HIIT, is recommended. The primary limitations of this review include its narrative design and the potential for publication bias; therefore, future large-scale randomized controlled trials across diverse populations are warranted.