{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:11:04Z","timestamp":1790244664834,"version":"4.1.0"},"reference-count":86,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Obesity and unhealthy dietary habits are among the leading modifiable determinants of cardiovascular disease, acting through biological mechanisms that extend far beyond excess body weight. Adipose tissue dysfunction, chronic low-grade inflammation, oxidative stress, endothelial impairment, mitochondrial dysfunction, and gut microbiota dysbiosis contribute to the development and progression of cardiometabolic disease. Consequently, nutrition should be regarded as a key biological modulator of cardiovascular risk, capable of influencing multiple interconnected metabolic and molecular pathways. Methods: This narrative review provides a critical and translational overview of the current evidence linking diet, obesity, and cardiovascular disease. We critically evaluated epidemiological studies, landmark randomized controlled trials, prospective cohort studies, meta-analyses, international guidelines, and relevant mechanistic investigations to examine the impact of major dietary patterns, obesity-related immunometabolic alterations, and emerging precision nutrition strategies on cardiovascular prevention and management. Results: Among currently available dietary models, the Mediterranean diet has one of the most extensive randomized evidence bases for cardiovascular prevention, including trials demonstrating reductions in major adverse cardiovascular events and other clinically relevant cardiovascular outcomes. Other healthy dietary patterns, including the Dietary Approaches to Stop Hypertension (DASH), healthy plant-based, and Nordic diets, consistently improve intermediate cardiometabolic outcomes, although evidence for hard cardiovascular endpoints is less robust. Conversely, Western dietary patterns characterized by high consumption of ultra-processed foods are associated with visceral adiposity, insulin resistance, vascular inflammation, mitochondrial dysfunction, endothelial injury, and increased cardiovascular risk. Conclusions: Contemporary evidence supports nutrition as a cornerstone of cardiovascular prevention and obesity management, with benefits may extend beyond weight reduction through modulation of key biological pathways involved in cardiometabolic disease.<\/jats:p>","DOI":"10.3390\/jcm15197428","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:07:54Z","timestamp":1790240874000},"page":"7428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diet, Obesity and Cardiovascular Health: Molecular Mechanisms, Clinical Evidence and Future Perspectives"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7781-9944","authenticated-orcid":false,"given":"Francesca","family":"Marino","sequence":"first","affiliation":[{"name":"Department of Educational, Psychological and Communication Sciences, University Suor Orsola Benincasa, 80135 Naples, Italy"},{"name":"UNESCO Chair \u201cEducation for Health and Sustainable Development\u201d, University of Naples Federico II, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1877-8550","authenticated-orcid":false,"given":"Maria Teresa","family":"Savo","sequence":"additional","affiliation":[{"name":"PhD Program in Translation Specialistic Medicine \u201cG.B. Morgagni\u201d, Curriculum \u201cCardiovascular Sciences\u201d, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9390-7263","authenticated-orcid":false,"given":"Dan Alexandru","family":"Cozac","sequence":"additional","affiliation":[{"name":"Physiology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Galzerano","sequence":"additional","affiliation":[{"name":"Heart Centre of Excellence, King Faisal Specialist Hospital & Research Center, 12713 Riyadh, Saudi Arabia"},{"name":"College of Medicine, Alfaisal University, 11533 Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed El","family":"Sabah","sequence":"additional","affiliation":[{"name":"Heart Centre of Excellence, King Faisal Specialist Hospital & Research Center, 12713 Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5192-6280","authenticated-orcid":false,"given":"Gabriele","family":"Cordoni","sequence":"additional","affiliation":[{"name":"Department of Heart, Lungs and Vessels, Montpellier University Hospital, CHU Arnaud de Villeneuve, 34000 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Tansella","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Mater Dei Hospital, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Martina","family":"Palmisano","sequence":"additional","affiliation":[{"name":"Department of Cardio-Thoracic Sciences and Public Health, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naji","family":"Kholaif","sequence":"additional","affiliation":[{"name":"Heart Centre of Excellence, King Faisal Specialist Hospital & Research Center, 12713 Riyadh, Saudi Arabia"},{"name":"College of Medicine, Alfaisal University, 11533 Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dania","family":"Mohty","sequence":"additional","affiliation":[{"name":"Heart Centre of Excellence, King Faisal Specialist Hospital & Research Center, 12713 Riyadh, Saudi Arabia"},{"name":"College of Medicine, Alfaisal University, 11533 Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0305-0113","authenticated-orcid":false,"given":"Giovanni","family":"Di Salvo","sequence":"additional","affiliation":[{"name":"Paedriatic Cardiology Unit, Department of Woman\u2019s and Child\u2019s Health, University Hospital of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani Al","family":"Sergani","sequence":"additional","affiliation":[{"name":"Heart Centre of Excellence, King Faisal Specialist Hospital & Research Center, 12713 Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3317-7342","authenticated-orcid":false,"given":"Valeria","family":"Pergola","sequence":"additional","affiliation":[{"name":"Heart Centre of Excellence, King Faisal Specialist Hospital & Research Center, 12713 Riyadh, Saudi Arabia"},{"name":"College of Medicine, Alfaisal University, 11533 Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1093\/eurheartj\/ehab484","article-title":"2021 ESC Guidelines on cardiovascular disease prevention in clinical practice","volume":"42","author":"Visseren","year":"2021","journal-title":"Eur. 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