Metabolic Dysfunction-Associated Steatotic Liver Disease and Cardiovascular Disease: An Integrated Narrative Review from Molecular Mechanisms to Nutritional and Bioactive Strategies

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the hepatic manifestation of systemic metabolic dysfunction and serves as an independent risk factor for cardiovascular disease (CVD), the primary cause of mortality in affected individuals. Rather than separate entities, MASLD and CVD share interconnected pathogenic mechanisms establishing a bidirectional liver–heart axis. This narrative review aims to provide an interdisciplinary overview integrating biochemistry, nutrition, and chemistry to elucidate these molecular pathways, circulating biomarkers, and natural bioactive strategies. Methods: A comprehensive literature synthesis was conducted, analyzing recent clinical and translational evidence regarding redox biology, metabolomics, lipidomics, immunometabolism, and nutritional interventions targeting the liver–heart axis in MASLD and CVD. Results: The liver–heart interaction is driven by shared processes, including insulin resistance, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, endothelial impairment, and immune remodeling. Omics technologies—specifically lipidomics and metabolomics—have unraveled distinct molecular signatures and circulating biomarkers, enabling earlier diagnosis and risk stratification. Furthermore, dietary interventions, functional foods, and naturally derived bioactive molecules demonstrate significant capacity to beneficially modulate these shared pathological cascades, supporting their role as complementary cardiometabolic risk reduction strategies. Conclusions: Elucidating the molecular crosstalk within the liver–heart axis underscores its critical role in cardiometabolic health. Targeting these shared pathways through naturally derived bioactives, integrated with precision nutrition and personalized therapeutic approaches, offers promising strategies for disease management.