Next Article in Journal
Development and Exploratory Evaluation of the Dietary Plastic Exposure Score for Mexican Populations in University Students
Previous Article in Journal
Nutritional Risk Among Emergency Department Patients with Diabetes Mellitus or Chronic Kidney Disease: A Single-Center Prospective Observational Comparative Study
Previous Article in Special Issue
Hydroxysafflor Yellow A Regulates SIRT1-FOXO3-BNIP3 Signaling Pathway to Promote Mitophagy: A Novel Therapeutic Strategy for Myocardial Ischemia-Reperfusion Injury
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Nutrients
Volume 18
Issue 14
10.3390/nu18142239
nutrients-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Review

Diet-Induced Ceramide Remodeling as a Mechanistic Link to Cardiac Metabolic Dysfunction

by
Manuela Giovanna Basilicata
1,
Lucia Scisciola
1,
Federico Capone
2,3,
Elisabetta Trevellin
2,
Pasquale Paolisso
4,5,
Marta Belmonte
4,5,
Ludovica Vittoria Marfella
1,
Martina Zanzillo
1,
Lorenzo Sabbatino
1,
Luigi De Rosa
1,
Nicola Celardo
1,
Mario Acunto
1,
Ada Pesapane
1,
Rosaria Anna Fontanella
1,
Nunzia Balzano
1,
Nicoletta Lettera
1,
Alberta Maria Maddalena Palazzo
1,
Giovanni Tortorella
1,
Rashmi Joshi
1,
Asad Zia
1,
Zeeshan Ulfat
1,
Maryam Arshad
1,
Paola Fioretto
3,
Giuseppe Paolisso
1,6 and
Michelangela Barbieri
1,*add Show full author list remove Hide full author list
1
Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
2
Unit of Internal Medicine III, Department of Medicine (DIMED), Padua University Hospital, University of Padua, 35128 Padua, Italy
3
Department of Biomedical Sciences, University of Padova, 35122 Padua, Italy
4
Cardiology Unit, Sant’Andrea University Hospital, 00189 Rome, Italy
5
Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy
6
UniCamillus International University of Health Sciences, 00161 Rome, Italy
*
Author to whom correspondence should be addressed.
Nutrients 2026, 18(14), 2239; https://doi.org/10.3390/nu18142239
Submission received: 3 June 2026 / Revised: 3 July 2026 / Accepted: 7 July 2026 / Published: 9 July 2026
(This article belongs to the Special Issue Molecular Mechanisms of Diet-Associated Cardiac Metabolism)
Versions Notes

Abstract

Background/Objectives: Dietary patterns characterized by excess saturated fat intake contribute to obesity, type 2 diabetes, and cardiac metabolic dysfunction. Ceramides, bioactive sphingolipids synthesized in response to nutrient overload, have emerged as key molecular mediators linking dietary lipid composition to alterations in cardiac metabolic signaling. This review aims to integrate current evidence on diet-induced ceramide remodeling and its impact on intracellular pathways regulating cardiac metabolism. Methods: We analyzed experimental and clinical studies investigating the effects of high-fat and Western-type diets on myocardial ceramide synthesis, lipidomic remodeling, and downstream signaling pathways. Evidence from animal models, genetic and pharmacological interventions, nutritional studies, and circulating biomarker analyses was examined to delineate mechanistic and translational insights. Results: Saturated fatty acid excess, particularly palmitate, activates the de novo ceramide synthesis pathway in the myocardium, promoting accumulation of specific ceramide species. This remodeling impairs insulin signaling through Akt inhibition, protein phosphatase 2A activation, and PKCζ-dependent mechanisms, contributing to cardiac metabolic inflexibility. Ceramides further disrupt mitochondrial function by altering electron transport chain activity, increasing reactive oxygen species production, and modulating mitophagy and apoptotic signaling. Lipidomic studies highlight species-specific effects, with C16-ceramides frequently associated with adverse metabolic and cardiovascular outcomes, whereas very-long-chain ceramides may exert distinct functional roles. Circulating ceramide profiles have also been linked to diet-associated cardiovascular risk. Conclusions: Diet-induced ceramide remodeling represents a central molecular axis connecting dietary lipid excess to altered cardiac metabolic signaling. Targeting sphingolipid metabolism through nutritional or pharmacological strategies may offer novel opportunities for preventing and managing diet-associated cardiac dysfunction.
Keywords: ceramides; sphingolipid metabolism; cardiac metabolic dysfunction ceramides; sphingolipid metabolism; cardiac metabolic dysfunction

Share and Cite

MDPI and ACS Style

Basilicata, M.G.; Scisciola, L.; Capone, F.; Trevellin, E.; Paolisso, P.; Belmonte, M.; Marfella, L.V.; Zanzillo, M.; Sabbatino, L.; De Rosa, L.; et al. Diet-Induced Ceramide Remodeling as a Mechanistic Link to Cardiac Metabolic Dysfunction. Nutrients 2026, 18, 2239. https://doi.org/10.3390/nu18142239

AMA Style

Basilicata MG, Scisciola L, Capone F, Trevellin E, Paolisso P, Belmonte M, Marfella LV, Zanzillo M, Sabbatino L, De Rosa L, et al. Diet-Induced Ceramide Remodeling as a Mechanistic Link to Cardiac Metabolic Dysfunction. Nutrients. 2026; 18(14):2239. https://doi.org/10.3390/nu18142239

Chicago/Turabian Style

Basilicata, Manuela Giovanna, Lucia Scisciola, Federico Capone, Elisabetta Trevellin, Pasquale Paolisso, Marta Belmonte, Ludovica Vittoria Marfella, Martina Zanzillo, Lorenzo Sabbatino, Luigi De Rosa, and et al. 2026. "Diet-Induced Ceramide Remodeling as a Mechanistic Link to Cardiac Metabolic Dysfunction" Nutrients 18, no. 14: 2239. https://doi.org/10.3390/nu18142239

APA Style

Basilicata, M. G., Scisciola, L., Capone, F., Trevellin, E., Paolisso, P., Belmonte, M., Marfella, L. V., Zanzillo, M., Sabbatino, L., De Rosa, L., Celardo, N., Acunto, M., Pesapane, A., Fontanella, R. A., Balzano, N., Lettera, N., Palazzo, A. M. M., Tortorella, G., Joshi, R., ... Barbieri, M. (2026). Diet-Induced Ceramide Remodeling as a Mechanistic Link to Cardiac Metabolic Dysfunction. Nutrients, 18(14), 2239. https://doi.org/10.3390/nu18142239

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop