{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:08:00Z","timestamp":1790111280363,"version":"4.0.1"},"reference-count":110,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity is a complex metabolic disorder resulting from interactions among genetic, environmental, and dietary factors. Traditional clinical markers may provide limited insight into the biochemical mechanisms that link nutrition and metabolic dysfunction; in this context, the epigenetic mechanisms through which nutrients modulate gene expression are central to understanding metabolic homeostasis. This review summarizes the published evidence on nutrient-driven epigenetic processes in obesity, focusing on DNA methyl donors, such as folate, vitamin B12, choline, betaine, serine, and methionine, and their effects on methylation and DNA methyltransferase activity. Metabolites such as acetyl-CoA, NAD+, and short-chain fatty acids (SCFAs) can also influence histone modifications, while diet-responsive microRNAs can regulate networks involved in adipogenesis, lipid metabolism, inflammation, and insulin signaling. Recent studies have identified epigenetic signatures associated with adiposity and metabolic traits, many of which are linked to the risk of cardiometabolic disease. This review is structured around the concept that nutrient-sensitive epigenetic mechanisms act as candidate biomarkers, linking dietary exposure to metabolic dysfunction. Recent evidence supports the idea that nutrient\u2013epigenetic variation could complement traditional metabolic evaluations by offering mechanistic insight and translational direction. These findings suggest that nutrient-sensitive epigenetic mechanisms are biologically plausible candidate biomarker layers; however, their clinical implementation is currently limited by issues including tissue specificity, reproducibility, and the need for prospective validation.<\/jats:p>","DOI":"10.3390\/ijms27104372","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T16:27:56Z","timestamp":1778776076000},"page":"4372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nutrient-Sensitive Epigenetic Modifiers as Candidate Biomarkers of Metabolic Dysfunction in Obesity: A Nutrigenomic Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5526-0489","authenticated-orcid":false,"given":"Diana","family":"Rodr\u00edguez-Vera","sequence":"first","affiliation":[{"name":"Section of Postgraduate Studies and Research, Higher School of Medicine, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Mexico City 11340, Mexico"},{"name":"B\u00e9ke Specialized Nutrition Clinic, Texcoco 56130, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9460-0848","authenticated-orcid":false,"given":"Manuel Abraham","family":"G\u00f3mez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Public Health Department, Faculty of Medicine, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Escolar 411A, Copilco Universidad, Coyoac\u00e1n, Mexico City 04360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mildred Valeria","family":"Herrera-Picazo","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina de Conservaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana Anguiano","family":"Robledo","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology Laboratory, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Mexico City 07738, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Tufi\u00f1o","sequence":"additional","affiliation":[{"name":"Pregnancy Pharmacology Laboratory, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia C.","family":"Bustamante-Tenorio","sequence":"additional","affiliation":[{"name":"B\u00e9ke Specialized Nutrition Clinic, Texcoco 56130, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6529-1502","authenticated-orcid":false,"given":"Marvin A.","family":"Soriano-Urs\u00faa","sequence":"additional","affiliation":[{"name":"Section of Postgraduate Studies and Research, Higher School of Medicine, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2920-8078","authenticated-orcid":false,"given":"\u00c1ngel","family":"Morales-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Escuela Superior de Computo, Instituto Polit\u00e9cnico Nacional, \u201cA. L\u00f3pez Mateos\u201d Professional Unit, Mexico City 07738, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2264-4598","authenticated-orcid":false,"given":"Eduardo Osiris","family":"Madrigal-Santill\u00e1n","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina de Conservaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arely","family":"Vergara-Casta\u00f1eda","sequence":"additional","affiliation":[{"name":"Promotion and Education for Health and Food Research Group, Chemical Sciences School, Universidad La Salle, Benjamin Franklin No. 47 Col. Condesa, Mexico City 06140, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5980-0980","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"Morales-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina de Conservaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","first-page":"167","article-title":"Papel de la epigen\u00e9tica en la nutrici\u00f3n y medicina de precisi\u00f3n para el tratamiento y prevenci\u00f3n de la obesidad","volume":"XVII","author":"Crujeiras","year":"2023","journal-title":"Nutr. Clin. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.trsl.2016.07.002","article-title":"Genome-wide DNA methylation pattern in visceral adipose tissue differentiates insulin-resistant from insulin-sensitive obese subjects","volume":"178","author":"Crujeiras","year":"2016","journal-title":"Transl. Res."},{"key":"ref_3","first-page":"e80418","article-title":"Epigenetic Mechanisms in the Transfer of Metabolic Disorders: A Comprehensive Review","volume":"17","author":"Swath","year":"2025","journal-title":"Cureus"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Contreras, R.E., Schriever, S.C., and Pfluger, P.T. (2019). Physiological and Epigenetic Features of Yoyo Dieting and Weight Control. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.01015"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Farzand, A., Rohin, M.A.K., Awan, S.J., Ahmad, A.M.R., Akram, H., Saleem, T., and Imran, M.M. (2025). Nutrigenomics of Obesity: Integrating Genomics, Epigenetics, and Diet\u2013Microbiome Interactions for Precision Nutrition. Life, 15.","DOI":"10.3390\/life15111658"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41392-024-01954-6","article-title":"Metabolic regulation of the immune system in health and diseases: Mechanisms and interventions","volume":"9","author":"Hu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13072-025-00640-3","article-title":"DNA methylation reshapes the expression of adipokines and adipose factors in white adipose tissues","volume":"18","author":"Fang","year":"2025","journal-title":"Epigenet. Chromatin"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"304","DOI":"10.7570\/jomes20131","article-title":"Leptin DNA Methylation and Its Association with Metabolic Risk Factors in a Northwest Indian Obese Population","volume":"30","author":"Sadashiv","year":"2021","journal-title":"J. Obes. Metab. Syndr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00011-020-01425-y","article-title":"Epigenetic signatures underlying inflammation: An interplay of nutrition, physical activity, metabolic diseases, and environmental factors for personalized nutrition","volume":"70","author":"Milagro","year":"2021","journal-title":"Inflamm. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1002\/1873-3468.70039","article-title":"The power of microRNA regulation-insights into immunity and metabolism","volume":"599","author":"Oliveto","year":"2025","journal-title":"FEBS Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ajhg.2022.12.014","article-title":"Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI","volume":"110","author":"Do","year":"2023","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1093\/advances\/nmac038","article-title":"Epigenetic Effects of Healthy Foods and Lifestyle Habits from the Southern European Atlantic Diet Pattern: A Narrative Review","volume":"13","author":"Lorenzo","year":"2022","journal-title":"Adv. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ostaiza-Cardenas, J., Tobar, A.C., Costa, S.C., Calero, D.S., L\u00f3pez-Carrera, A., Berm\u00fadez, F.G., and Orellana-Manzano, A. (2025). Epigenetic modulation by life-style: Advances in diet, exercise, and mindfulness for disease prevention and health optimization. Front. Nutr., 21.","DOI":"10.3389\/fnut.2025.1632999"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105457","DOI":"10.1016\/j.jbc.2023.105457","article-title":"Regulatory mechanisms of one-carbon metabolism enzymes","volume":"299","author":"Petrova","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lyon, P., Strippoli, V., Fang, B., and Cimmino, L. (2020). B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease. Nutrients, 12.","DOI":"10.3390\/nu12092867"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sfakianoudis, K., Zikopoulos, A., Grigoriadis, S., Seretis, N., Maziotis, E., Anifandis, G., Xystra, P., Kostoulas, C., Giougli, U., and Pantos, K. (2024). The Role of One-Carbon Metabolism and Methyl Donors in Medically Assisted Reproduction: A Narrative Review of the Literature. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094977"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.tem.2021.05.011","article-title":"One carbon metabolism and early development: A diet-dependent destiny","volume":"32","author":"Korsmo","year":"2021","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3945\/an.111.000992","article-title":"Folate and DNA methylation: A review of molecular mechanisms and the evidence for folate\u2019s role","volume":"3","author":"Crider","year":"2012","journal-title":"Adv. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/nyas.12956","article-title":"One-carbon metabolism and epigenetics: Understanding the specificity","volume":"1363","author":"Mentch","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Korsmo, H.W., Dave, B., Trasino, S., Saxena, A., Liu, J., Caviglia, J.M., Edwards, K., Dembitzer, M., Sheeraz, S., and Khaldi, S. (2022). Maternal Choline Supplementation and High-Fat Feeding Interact to Influence DNA Methylation in Offspring in a Time-Specific Manner. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.841787"},{"key":"ref_21","first-page":"159","article-title":"PPARGC1A promoter DNA-methylation level and glucose metabolism in Ecuadorian women with Turner syndrome","volume":"42","author":"Salinas","year":"2020","journal-title":"Horm. Mol. Biol. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e72359","DOI":"10.7554\/eLife.72359","article-title":"Constitutive loss of DNMT3A causes morbid obesity through misregulation of adipogenesis","volume":"11","author":"Tovy","year":"2022","journal-title":"eLife"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e30766","DOI":"10.7554\/eLife.30766","article-title":"Dnmt3a is an epigenetic mediator of adipose insulin resistance","volume":"6","author":"You","year":"2017","journal-title":"eLife"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ma\u0142odobra-Mazur, M., Cierzniak, A., Kaliszewski, K., and Dobosz, T. (2021). PPARG Hypermethylation as the First Epigenetic Modification in Newly Onset Insulin Resistance in Human Adipocytes. Genes, 12.","DOI":"10.3390\/genes12060889"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"N\u00fa\u00f1ez-S\u00e1nchez, M.\u00c1., Jim\u00e9nez-M\u00e9ndez, A., Su\u00e1rez-Cort\u00e9s, M., Mart\u00ednez-S\u00e1nchez, M.A., S\u00e1nchez-Sol\u00eds, M., Blanco-Carnero, J.E., Ruiz-Alcaraz, A.J., and Ramos-Molina, B. (2023). Inherited Epigenetic Hallmarks of Childhood Obesity Derived from Prenatal Exposure to Obesogens. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20064711"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/s41392-024-01918-w","article-title":"Crossing epigenetic frontiers: The intersection of novel histone modifications and diseases","volume":"9","author":"Yao","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41392-025-02141-x","article-title":"Energy metabolism in health and diseases","volume":"10","author":"Liu","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-022-01257-8","article-title":"The sirtuin family in health and disease","volume":"7","author":"Wu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fortuny, L., and Sebasti\u00e1n, C. (2021). Sirtuins as Metabolic Regulators of Immune Cells Phenotype and Function. Genes, 12.","DOI":"10.3390\/genes12111698"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e70657","DOI":"10.1111\/cns.70657","article-title":"AMPK\/SIRT1\/PGC-1\u03b1 Signaling Pathway: Molecular Mechanisms and Targeted Strategies From Energy Homeostasis Regulation to Disease Therapy","volume":"31","author":"Chen","year":"2025","journal-title":"CNS Neurosci. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Veerapaneni, P., Goo, B., Ahmadieh, S., Shi, H., Kim, D.S., Ogbi, M., Cave, S., Chouhaita, R., Cyriac, N., and Fulton, D.J. (2024). Transgenic Overexpression of HDAC9 Promotes Adipocyte Hypertrophy, Insulin Resistance and Hepatic Steatosis in Aging Mice. Biomolecules, 14.","DOI":"10.3390\/biom14040494"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Du, Y., He, C., An, Y., Huang, Y., Zhang, H., Fu, W., Wang, M., Shan, Z., Xie, J., and Yang, Y. (2024). The Role of Short Chain Fatty Acids in Inflammation and Body Health. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137379"},{"key":"ref_33","first-page":"16","article-title":"Microbial short chain fatty acids: Effective histone deacetylase inhibitors in immune regulation (Review)","volume":"57","author":"Wang","year":"2026","journal-title":"Int. J. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e30344","DOI":"10.1097\/MD.0000000000030344","article-title":"Role of EZH2 in adipogenesis and obesity: Current state of the art and implications\u2014A review","volume":"101","author":"Wang","year":"2022","journal-title":"Medicine"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wen, W., Gu, S., Guo, F., Chen, Z., Yan, S., and Mo, Z. (2025). Dynamic Rendition of Adipose Genes Under Epigenetic Regulation: Revealing New Mechanisms of Obesity Occurrence. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47070540"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ding, S., and Wang, P. (2025). The Life of MicroRNAs: Biogenesis, Function and Decay in Cancer. Biomolecules, 15.","DOI":"10.20944\/preprints202509.0413.v1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1002\/ame2.70076","article-title":"Advances in miRNA research: Unraveling the complexities of gene regulation","volume":"8","author":"Zheng","year":"2025","journal-title":"Anim. Models Exp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2012606","DOI":"10.15252\/emmm.202012606","article-title":"miR-33 in cardiometabolic diseases: Lessons learned from novel animal models and approaches","volume":"13","author":"Price","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Peng, Y., Liu, A., Zhu, Q., Liu, X., Cai, B., Yan, Z., Gao, J., Zhu, R., and Wang, C. (2025). Advances in the Regulation of Lipid Metabolism by Non-Coding RNAs. Animals, 15.","DOI":"10.3390\/ani15172621"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Locatelli, C., Luz, K., Andrade, S.F.d., Bellaver, E.H., Ogoshi, R.C.S., Centa, A., Assolini, J.P., Pont, G.C.D., and Creczynski-Pasa, T.B. (2026). MicroRNAs as Key Regulators in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Bioinformatics Analysis. Biomedicines, 14.","DOI":"10.3390\/biomedicines14010120"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e1899","DOI":"10.1210\/clinem\/dgac023","article-title":"Circulating Levels of microRNA-122 and Hepatic Fat Change in Response to Weight-Loss Interventions: CENTRAL Trial","volume":"107","author":"Wang","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3892\/ijmm.2025.5668","article-title":"Metabolic dysfunction-associated steatotic liver disease: Pathogenesis, model and treatment (Review)","volume":"56","author":"Ma","year":"2025","journal-title":"Int. J. Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gusev, E., Sarapultsev, A., and Zhuravleva, Y. (2026). Insulin Resistance and Inflammation. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27031237"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"25168657221130041","DOI":"10.1177\/25168657221130041","article-title":"Therapeutic Potential of miRNAs for Type 2 Diabetes Mellitus: An Overview","volume":"15","author":"Palihaderu","year":"2022","journal-title":"Epigenet. Insights"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.7150\/ijbs.59876","article-title":"miR-223: An Effective Regulator of Immune Cell Differentiation and Inflammation","volume":"17","author":"Jiao","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kappeler, L. (2022). Role of Adipose Tissue microRNAs in the Onset of Metabolic Diseases and Implications in the Context of the DOHaD. Cells, 11.","DOI":"10.3390\/cells11233711"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"DeLucas, M., S\u00e1nchez, J., Palou, A., and Serra, F. (2024). The Impact of Diet on miRNA Regulation and Its Implications for Health: A Systematic Review. Nutrients, 16.","DOI":"10.3390\/nu16060770"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100712","DOI":"10.1016\/j.jnha.2025.100712","article-title":"Diet, nutrition, and healthy aging: Are miRNAs the link? A narrative review","volume":"29","author":"Elliott","year":"2025","journal-title":"J. Nutr. Health Aging"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Syding, L.A., Nickl, P., Kasparek, P., and Sedlacek, R. (2020). CRISPR\/Cas9 Epigenome Editing Potential for Rare Imprinting Diseases: A Review. Cells, 9.","DOI":"10.3390\/cells9040993"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Garc\u00eda, I., Grisotto, G., Heini, A., Gibertoni, S., Nussl\u00e9, S., Gonseth, N.S., and Donica, O. (2024). Examining nutrition strategies to influence DNA methylation and epigenetic clocks: A systematic review of clinical trials. Front. Aging, 5.","DOI":"10.3389\/fragi.2024.1417625"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nature20784","article-title":"Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity","volume":"541","author":"Wahl","year":"2017","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/s12935-022-02719-3","article-title":"Disease-associated regulation of gene expression by resveratrol: Special focus on the PI3K\/AKT signaling pathway","volume":"22","author":"Bahroudi","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hassan, F.U., Rehman, M.S., Khan, M.S., Ali, M.A., Javed, A., Nawaz, A., and Yang, C. (2019). Curcumin as an Alternative Epigenetic Modulator: Mechanism of Action and Potential Effects. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00514"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Reva, K., Laranjinha, J., and Rocha, B. (2023). Epigenetic Modifications Induced by the Gut Microbiota May Result from What We Eat: Should We Talk About Precision Diet in Health and Disease?. Metabolites, 13.","DOI":"10.3390\/metabo13030375"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e496","DOI":"10.1002\/mco2.496","article-title":"Epigenetic modifications in obesity-associated diseases","volume":"5","author":"Long","year":"2024","journal-title":"MedComm"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"103013","DOI":"10.1016\/j.redox.2023.103013","article-title":"Endothelial TET2 regulates the white adipose browning and metabolism via fatty acid oxidation in obesity","volume":"69","author":"Yefei","year":"2024","journal-title":"Redox Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41366-020-00729-7","article-title":"DNA methylation in adipocytes from visceral and subcutaneous adipose tissue influences insulin-signaling gene expression in obese individuals","volume":"45","author":"Cierzniak","year":"2021","journal-title":"Int. J. Obes."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Sun, Q.F., Tang, L.J., Wang, M.J., Zhu, P.W., Li, Y.Y., Ma, H.L., Huang, O.Y., Hong, L., Li, G., and Byrne, C.D. (2022). Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients with Biopsy-Proven Non-Alcoholic Fatty Liver Disease. Front. Med., 9.","DOI":"10.3389\/fmed.2022.864570"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Obradovic, M., Sudar-Milovanovic, E., Soskic, S., Essack, M., Arya, S., Stewart, A.J., Gojobori, T., and Isenovic, E.R. (2021). Leptin and Obesity: Role and Clinical Implication. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.585887"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"B\u0142a\u017cejewska, W., D\u0105browska, J., Micha\u0142owska, J., and Bogda\u0144ski, P. (2025). The Role of Adiponectin and ADIPOQ Variation in Metabolic Syndrome: A Narrative Review. Genes, 16.","DOI":"10.3390\/genes16060699"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1038\/s41467-023-38439-z","article-title":"Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes","volume":"14","author":"McAllan","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"M\u0142ynarska, E., Bojdo, K., Bulicz, A., Frankenstein, H., G\u0105sior, M., Kustosik, N., Rysz, J., and Franczyk, B. (2025). Obesity as a Multifactorial Chronic Disease: Molecular Mechanisms, Systemic Impact, and Emerging Digital Interventions. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47100787"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1093\/aje\/kwy025","article-title":"An Epigenome-Wide Association Study of Obesity-Related Traits","volume":"187","author":"Dhana","year":"2018","journal-title":"Am. J. Epidemiol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Nohesara, S., Mostafavi Abdolmaleky, H., Pirani, A., Pettinato, G., and Thiagalingam, S. (2025). The Obesity\u2013Epigenetics\u2013Microbiome Axis: Strategies for Therapeutic Intervention. Nutrients, 17.","DOI":"10.3390\/nu17091564"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Mierziak, J., Kostyn, K., Boba, A., Czemplik, M., Kulma, A., and Wojtasik, W. (2021). Influence of the Bioactive Diet Components on the Gene Expression Regulation. Nutrients, 13.","DOI":"10.3390\/nu13113673"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"155594","DOI":"10.1016\/j.metabol.2023.155594","article-title":"A polyphenol-rich green Mediterranean diet enhances epigenetic regulatory potential: The DIRECT PLUS randomized controlled trial","volume":"145","author":"Hoffmann","year":"2023","journal-title":"Metabolism"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1186\/s12944-019-1120-6","article-title":"Fatty acids, epigenetic mechanisms and chronic diseases: A systematic review","volume":"18","author":"Milagro","year":"2019","journal-title":"Lipids Health Dis."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Konjar, \u0160., Benedik, E., \u0160estan, M., Veldhoen, M., and \u017dupanic, A. (2025). Systems biology to unravel Western diet-associated triggers in inflammatory bowel disease. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1621334"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s12986-025-00947-8","article-title":"The effects of the mediterranean diet supplemented with olive oils on pro-inflammatory biomarkers and soluble adhesion molecules: A systematic review and meta-analysis of randomized controlled trials","volume":"22","author":"Tehrani","year":"2025","journal-title":"Nutr. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1007\/s11357-025-01835-y","article-title":"Lower diet quality accelerates DNA methylation-based age","volume":"48","author":"Shen","year":"2026","journal-title":"GeroScience"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1161\/HYPERTENSIONAHA.123.22334","article-title":"Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure","volume":"81","author":"Guirette","year":"2024","journal-title":"Hypertension"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Dwaraka, V.B., Aronica, L., Carreras-Gallo, N., Robinson, J.L., Hennings, T., Carter, M.M., Corley, M.J., Lin, A., Turner, L., and Smith, R. (2024). Unveiling the epigenetic impact of vegan vs. omnivorous diets on aging: Insights from the Twins Nutrition Study (TwiNS). BMC Med., 22.","DOI":"10.1186\/s12916-024-03513-w"},{"key":"ref_73","first-page":"994","article-title":"Dietary associations with reduced epigenetic age: A secondary data analysis of the methylation diet and lifestyle study","volume":"17","author":"Villanueva","year":"2025","journal-title":"Aging"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s10522-024-10121-x","article-title":"The influence of sex-specific factors on biological transformations and health outcomes in aging processes","volume":"25","author":"Huang","year":"2024","journal-title":"Biogerontology"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Mehta, V., Nagu, P., Inbaraj, B.S., Sharma, M., Parashar, A., and Sridhar, K. (2022). Epigenetics and Gut Microbiota Crosstalk: A Potential Factor in Pathogenesis of Cardiovascular Disorders. Bioeng, 9.","DOI":"10.3390\/bioengineering9120798"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.cell.2017.12.013","article-title":"Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming","volume":"172","author":"Christ","year":"2018","journal-title":"Cell"},{"key":"ref_77","first-page":"2636","article-title":"Can Nutritional Epigenomics Explain Persistent Effects of Periconceptional Folic Acid in the Methylome?","volume":"152","author":"Ward","year":"2023","journal-title":"J. Nutr."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.ajcnut.2023.10.006","article-title":"National Diet and Nutrition Survey data reveal a decline in folate status in the United Kingdom population between 2008 and 2019","volume":"118","author":"Jones","year":"2023","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2293410","DOI":"10.1080\/15592294.2023.2293410","article-title":"Impact of folic acid supplementation on the epigenetic profile in healthy unfortified individuals\u2014A randomized intervention trial","volume":"19","author":"Michels","year":"2024","journal-title":"Epigenetics"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3153","DOI":"10.1007\/s10068-024-01664-3","article-title":"Fatty acids and epigenetics in health and diseases","volume":"33","author":"Chung","year":"2024","journal-title":"Food Sci. Biotechnol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s13073-020-00810-w","article-title":"DNA methylation and body mass index from birth to adolescence: Meta-analyses of epigenome-wide association studies","volume":"12","author":"Vehmeijer","year":"2020","journal-title":"Genome Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s13148-021-01162-x","article-title":"Impact of BMI and waist circumference on epigenome-wide DNA methylation and identification of epigenetic biomarkers in blood: An EWAS in multi-ethnic Asian individuals","volume":"13","author":"Chen","year":"2021","journal-title":"Clin. Epigenet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/s41576-023-00580-2","article-title":"Methods and applications for single-cell and spatial multi-omics","volume":"24","author":"Vandereyken","year":"2023","journal-title":"Nat. Rev. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13045-024-01596-9","article-title":"Spatial multi-omics: Deciphering technological landscape of integration of multi-omics and its applications","volume":"17","author":"Liu","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/s41580-023-00615-w","article-title":"The technological landscape and applications of single-cell multi-omics","volume":"24","author":"Baysoy","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Rui, V. (2024). Transforming Clinical Research: The Power of High-Throughput Omics Integration. Proteomes, 12.","DOI":"10.3390\/proteomes12030025"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.21037\/tau-2025-328","article-title":"Single-cell multi-omics and spatial transcriptomics reveal the transcriptional regulatory landscape of clear cell renal cell carcinoma","volume":"14","author":"Duan","year":"2025","journal-title":"Transl. Androl. Urol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12263-025-00790-9","article-title":"Nutrigenomics meets multi-omics: Integrating genetic, metabolic, and microbiome data for personalized nutrition strategies","volume":"20","author":"Nourazarain","year":"2025","journal-title":"Genes Nutr."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1093\/jmcb\/mjab043","article-title":"Epigenetic regulation of energy metabolism in obesity","volume":"13","author":"Gao","year":"2021","journal-title":"J. Mol. Cell Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/s13148-024-01806-8","article-title":"Clinical promise and applications of epigenetic biomarkers","volume":"16","author":"Wisman","year":"2024","journal-title":"Clin. Epigenet."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Vo, D., and Trinh, K. (2024). Emerging Biomarkers in Metabolomics: Advancements in Precision Health and Disease Diagnosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252313190"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1021\/prechem.5c00014","article-title":"Advances in Epigenomic Sequencing and Their Applications in Cancer Diagnostics","volume":"3","author":"Lin","year":"2025","journal-title":"Precis. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1016\/j.clnu.2022.03.021","article-title":"Nutritional care is a human right: Translating principles to clinical practice","volume":"41","author":"Davisson","year":"2022","journal-title":"Nutr. Clin. Pract."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/jpen.1536","article-title":"RW-2018-Research Workshop: The Effect of Nutrition on Epigenetic Status, Growth, and Health","volume":"43","author":"Skinner","year":"2019","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Singar, S., Nagpal, R., Arjmandi, B.H., and Akhavan, N.S. (2024). Personalized Nutrition: Tailoring Dietary Recommendations Through Genetic Insights. Nutrients, 16.","DOI":"10.3390\/nu16162673"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jjcc.2020.02.003","article-title":"Developmental origins of health and disease theory in cardiology","volume":"76","author":"Yuichiro","year":"2020","journal-title":"J. Cardiol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Bokor, S., Vass, R.A., Funke, S., Ertl, T., and Moln\u00e1r, D. (2022). Epigenetic Effect of Maternal Methyl-Group Donor Intake on Offspring\u2019s Health and Disease. Life, 12.","DOI":"10.3390\/life12050609"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4873","DOI":"10.2147\/DMSO.S579409","article-title":"Maternal Nutrition, Toxicants, and Epigenetic Programming of Obesity Across Generations","volume":"18","author":"Alum","year":"2025","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2516865720981924","DOI":"10.1177\/2516865720981924","article-title":"Advances in Nutritional Epigenetics\u2014A Fresh Perspective for an Old Idea. Lessons Learned, Limitations, and Future Directions","volume":"13","author":"Sedley","year":"2020","journal-title":"Epigenet. Insights"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"109604","DOI":"10.1016\/j.jnutbio.2024.109604","article-title":"Interplay between maternal nutrition and epigenetic programming on offspring hypertension","volume":"127","author":"Tain","year":"2024","journal-title":"J. Nutr. Biochem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1111\/apa.16258","article-title":"Epigenetics provides a bridge between early nutrition and long-term health and a target for disease prevention","volume":"111","author":"Siddeek","year":"2022","journal-title":"Acta Paediatr."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Abraham, M.J., El Sherbini, A., El-Diasty, M., Askari, S., and Szewczuk, M. (2023). Restoring Epigenetic Reprogramming with Diet and Exercise to Improve Health-Related Metabolic Diseases. Biomolecules, 13.","DOI":"10.3390\/biom13020318"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Barr, E., Comtois-Cabana, M., Coope, A., Cot\u00e9, S.M., Kobor, M.S., Konwar, C., Lupien, S., Geoffroy, M.C., Boivin, M., and Proven\u00e7al, N. (2025). Early-Life Adversity and Epigenetic Aging: Findings from a 17-Year Longitudinal Study. Biomolecules, 15.","DOI":"10.3390\/biom15060887"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e1171","DOI":"10.1002\/prp2.1171","article-title":"Epigenetics in obesity: Mechanisms and advances in therapies based on natural products","volume":"12","author":"Chen","year":"2024","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Karakasis, P., Stachteas, P., Iliakis, P., Sidiropoulos, G., Grigoriou, K., Patoulias, D., Antoniadis, A.P., and Fragakis, N. (2026). Inflammation and Resolution in Obesity-Related Cardiovascular Disease. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27010535"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s41435-021-00124-w","article-title":"Epithelial sensing of microbiota-derived signals","volume":"22","author":"Eshleman","year":"2021","journal-title":"Genes Immun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1016\/j.immuni.2025.06.019","article-title":"Gasdermin-D-mediated epithelial-immune circuit synchronizes nutrient absorption and host defense in the small intestine","volume":"58","author":"Yu","year":"2025","journal-title":"Immunity"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/cei\/uxae004","article-title":"Revolutionizing immune research with organoid-based co-culture and chip systems","volume":"218","author":"Papp","year":"2024","journal-title":"Clin. Exp. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1016\/j.fmre.2023.11.014","article-title":"Single-cell epigenomics and proteomics methods integrated in multiomics","volume":"5","author":"Bi","year":"2025","journal-title":"Fundam. Res."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Li, X., and Qi, L. (2022). Epigenetics in Precision Nutrition. J. Pers. Med., 12.","DOI":"10.3390\/jpm12040533"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4372\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T16:32:27Z","timestamp":1778776347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":110,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104372"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104372","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]}}}