Mechanistic insights and evidence-based management of metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) through combined diet and exercise interventions: an evidence-based narrative review

Metabolic dysfunction–associated steatotic liver disease (MASLD; formerly NAFLD) is increasing worldwide, while management is constrained by limited effective pharmacotherapies and poor long-term adherence to lifestyle change. We synthesized mechanistic pathways and primary human interventional evidence on combined diet-plus-exercise strategies to inform lifestyle management. Evidence-based narrative review with a structured literature search and a predefined evidence framework. We prioritized primary human interventional studies (randomized or controlled trials when available) evaluating combined dietary and exercise interventions in MASLD/NAFLD; mechanistic studies were used for biological context. Reviews/meta-analyses were used only to summarize existing evidence and were not treated as additional primary studies. Owing to heterogeneity in interventions and outcomes, we performed qualitative synthesis (no de novo meta-analysis). Evidence indicates that combined dietary and exercise interventions exert synergistic effects on key metabolic and inflammatory pathways, including AMPK/SIRT1 activation, mitochondrial biogenesis, and gut–liver axis modulation, thereby improving hepatic steatosis and metabolic profiles more effectively than single interventions. Integrated dietary and exercise interventions appear more effective than diet- or exercise-only strategies for MASLD/NAFLD management. Individualized programs supported by digital health technologies and multi-omics profiling may further optimize lifestyle intervention delivery and move care toward a precision-oriented model.