Metabolic Dysfunction-Associated Steatotic Liver Disease and Cardiovascular Disease: An Integrated Narrative Review from Molecular Mechanisms to Nutritional and Bioactive Strategies
4 affiliations
- 1Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Via di Val Cannuta 247, 00166 Rome, Italy
- 2IRCCS San Raffaele Roma, 00166 Rome, Italy
- 3Pharmacy Department, Faculty of Medicine and Health Sciences, University of Science and Technology-Aden, Alshaab Street, Enmaa City 22003, Yemen
- 4Department of Pharmaceutical Sciences, University of Milan, Via Mangiagalli 25, 20133 Milan, Italy
Abstract
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.
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BibTeX
@article{castelli2026metabolic,
title = {{Metabolic Dysfunction-Associated Steatotic Liver Disease and Cardiovascular Disease: An Integrated Narrative Review from Molecular Mechanisms to Nutritional and Bioactive Strategies}},
author = {Serena Castelli and Gilda Aiello and Fares M. S. Muthanna and Carmen Lammi and Gianluca Tripodi and Vincenzo Aiello and Mauro Lombardo and Sara Baldelli},
journal = {Metabolites},
year = {2026},
month = nov,
doi = {10.3390/metabo16110855},
url = {https://www.mdpi.com/2218-1989/16/11/855},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Metabolic Dysfunction-Associated Steatotic Liver Disease and Cardiovascular Disease: An Integrated Narrative Review from Molecular Mechanisms to Nutritional and Bioactive Strategies
AU - Serena Castelli
AU - Gilda Aiello
AU - Fares M. S. Muthanna
AU - Carmen Lammi
AU - Gianluca Tripodi
AU - Vincenzo Aiello
AU - Mauro Lombardo
AU - Sara Baldelli
PY - 2026
DA - 2026/11/04
JO - Metabolites
DO - 10.3390/metabo16110855
UR - https://www.mdpi.com/2218-1989/16/11/855
AB - 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.
SN - 2218-1989
ER -