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The Roles of Diet and Nutrition in Metabolic Diseases: Advancements in Molecular Insights

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 May 2026 | Viewed by 6664

Special Issue Editor

Dr. Ramos-López Omar

E-Mail Website
Guest Editor
Medicine and Psychology School, Autonomous University of Baja California (UABC), Universidad 14418, Parque Internacional Industrial Tijuana, Tijuana 22390, BC, Mexico
Interests: nutrition; obesity; diet; chronic diseases; genetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolic diseases, including obesity, type 2 diabetes, cardiovascular disease, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease, constitute a global public health problem. In addition to sedentarism and emotional stress, diets high in fat, sugar, and sodium and deficient in fiber and essential micronutrients significantly contribute to the prevalence of these diseases. Advances in omics sciences, such as genomics (genetic background), epigenomics (epigenetic marks), metagenomics (gut microbiota composition), metabolomics (metabolic fingerprints), and proteomics (protein profiles), help to clarify the molecular mechanisms underlying the development of these pathologies and their relationship with diet and nutrition. These findings also enable the design of personalized intervention strategies to improve the nutritional management of metabolic diseases. This Special Issue covers observational or animal evidence pertaining to the impact of diet and nutrition on the occurrence of metabolic diseases, with an emphasis on molecular research. Clinical trials that focus on the use of dietary interventions for the treatment of metabolic diseases and incorporate molecular insights are welcome. We additionally seek comprehensive reviews that explore key advances in understanding the role of nutrition in metabolic diseases at the molecular level. Studies combining the use of different omics tools will particularly be considered.

Dr. Ramos-López Omar
Guest Editor

Manuscript Submission Information

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Keywords

  • diet
  • nutrition
  • metabolic diseases
  • obesity
  • genetics
  • microbiota
  • epigenetics
  • metabolomics

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Published Papers (4 papers)

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Research

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18 pages, 876 KB  
Article
Global Leukocyte DNA Methylation Is Associated with Dietary Methyl-Donor Intake and Cardiometabolic Risk in Rheumatoid Arthritis and Control Subjects
by Gerardo A. Macias, Bertha Campos-López, Karen Pesqueda-Cendejas, Paulina E. Mora-García, Eneida Turiján-Espinoza, Juan M. Vargas-Morales, Isela Parra-Rojas and Ulises De la Cruz-Mosso
Int. J. Mol. Sci. 2026, 27(3), 1578; https://doi.org/10.3390/ijms27031578 - 5 Feb 2026
Viewed by 504
Abstract
In rheumatoid arthritis (RA), altered DNA methylation patterns could be associated with pro-inflammatory, immune, and metabolic risk profiles. Notably, DNA methylation is dynamically regulated by the interplay of multiple factors, including diet, cardiometabolic status, and aging. Therefore, this study aimed to assess the [...] Read more.
In rheumatoid arthritis (RA), altered DNA methylation patterns could be associated with pro-inflammatory, immune, and metabolic risk profiles. Notably, DNA methylation is dynamically regulated by the interplay of multiple factors, including diet, cardiometabolic status, and aging. Therefore, this study aimed to assess the associations between global leukocyte DNA methylation, dietary methyl-donor intake, and cardiometabolic risk in RA and control subjects (CS). A cross-sectional study was conducted with 123 female RA patients classified by the 2010 ACR-EULAR criteria, and 130 female CS. Leukocyte DNA methylation status was assessed with the 5-mC DNA ELISA Kit. RA patients exhibited significantly lower global DNA methylation levels than those with CS. RA status was independently associated with lower DNA methylation levels after adjustment for age and body mass index. Similarly, in both study groups methionine intake showed an independent inverse association with global DNA methylation across adjusted models and lower methylation levels were consistently associated with an unfavorable cardiometabolic profile, characterized by increased adverse adiposity- and lipid-related indexes. In conclusion, RA patients exhibited lower global leukocyte DNA methylation levels compared with CS. In both study groups, lower DNA methylation levels were associated with low methionine intake and an unfavorable cardiometabolic profile. Full article
(This article belongs to the Special Issue The Roles of Diet and Nutrition in Metabolic Diseases: Advancements in Molecular Insights)
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12 pages, 385 KB  
Article
Interaction Between the UCP2 rs659366 Polymorphism and Dietary Capsaicin Intake in Relation to the Inflammatory State in Mexican Adults
by Ana Alondra Sobrevilla-Navarro, Bertha Landeros-Sanchez, Jose Roman Chavez-Mendez, Genaro Rodriguez-Uribe and Omar Ramos-Lopez
Int. J. Mol. Sci. 2025, 26(21), 10419; https://doi.org/10.3390/ijms262110419 - 27 Oct 2025
Viewed by 1197
Abstract
Metabolic diseases such as obesity and related conditions have an inflammatory basis. Genetic and nutritional factors can influence the development of these diseases by altering the inflammatory state. This study aimed to analyse how the rs659366 (G/A) polymorphism in the UCP2 gene interacts [...] Read more.
Metabolic diseases such as obesity and related conditions have an inflammatory basis. Genetic and nutritional factors can influence the development of these diseases by altering the inflammatory state. This study aimed to analyse how the rs659366 (G/A) polymorphism in the UCP2 gene interacts with dietary capsaicin (CAP) consumption and affects inflammatory markers in Mexican adults. A cross-sectional, analytical study was conducted in 212 adult patients. The UCP2 rs659366 polymorphism was genotyped using an allelic discrimination assay. Dietary CAP intake was measured with a validated food frequency questionnaire. Multivariate linear regression analyses were performed for interaction analyses. The ancestral allele G accounted for 40.2% and the risk allele A accounted for 59.8% of samples. There was a significant interaction between CAP intake and the UCP2 rs659366 polymorphism for the inflammatory marker NLR (neutrophil-to-lymphocyte ratio) (p < 0.05). Among subjects with the G allele, higher CAP intake was associated with higher NLR scores (p < 0.001). Patients with the G allele of the UCP2 rs659366 polymorphism experienced increased inflammation with higher CAP intake. This finding highlights the need for future studies in personalised nutrition and could expand knowledge about the effects of CAP on obesity and inflammation. Full article
(This article belongs to the Special Issue The Roles of Diet and Nutrition in Metabolic Diseases: Advancements in Molecular Insights)
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Review

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21 pages, 1052 KB  
Review
Vitamin D as a Regulator of the Biological Clock—Implications for Circadian–Metabolic Dysregulation
by Milena Vesković, Nikola Šutulović, Emilija Djuric, Dragan Hrnčić, Aleksandra Rašić Marković, Olivera Stanojlović and Dušan Mladenović
Int. J. Mol. Sci. 2026, 27(7), 3243; https://doi.org/10.3390/ijms27073243 - 2 Apr 2026
Viewed by 546
Abstract
Circadian disruption represents a global health issue associated with cardiometabolic diseases, sleep disturbances, and mood disorders, driven by a pathophysiological network including clock gene dysregulation and impaired melatonin synthesis. Vitamin D exerts pleiotropic effects on metabolic regulation, immune function, neurotransmission, and possibly circadian [...] Read more.
Circadian disruption represents a global health issue associated with cardiometabolic diseases, sleep disturbances, and mood disorders, driven by a pathophysiological network including clock gene dysregulation and impaired melatonin synthesis. Vitamin D exerts pleiotropic effects on metabolic regulation, immune function, neurotransmission, and possibly circadian synchronization. Emerging evidence suggests that vitamin D and its hydroxyderivatives modulate clock gene expression, influence transcriptional regulators such as retinoic acid receptor-related orphan receptors and REV-ERBs, and interact with melatonin synthesis and signaling. Vitamin D deficiency has been associated with metabolic syndrome, impaired sleep quality, and depression. Although interventional studies yield heterogeneous results, higher vitamin D status may confer protective metabolic and neurobehavioral effects. This review summarizes current evidence on the role of vitamin D in circadian disruption and evaluates its potential therapeutic relevance in circadian–metabolic dysregulation. Full article
(This article belongs to the Special Issue The Roles of Diet and Nutrition in Metabolic Diseases: Advancements in Molecular Insights)
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24 pages, 1426 KB  
Review
Dietary and Pharmacological Modulation of Aging-Related Metabolic Pathways: Molecular Insights, Clinical Evidence, and a Translational Model
by Antonio Fernando Murillo-Cancho, David Lozano-Paniagua and Bruno José Nievas-Soriano
Int. J. Mol. Sci. 2025, 26(19), 9643; https://doi.org/10.3390/ijms26199643 - 2 Oct 2025
Cited by 2 | Viewed by 3936
Abstract
Advances in geroscience suggest that aging is modulated by molecular pathways that are amenable to dietary and pharmacological intervention. We conducted an integrative critical review of caloric restriction (CR), intermittent fasting (IF), and caloric restriction mimetics (CR-mimetics) to compare shared mechanisms, clinical evidence, [...] Read more.
Advances in geroscience suggest that aging is modulated by molecular pathways that are amenable to dietary and pharmacological intervention. We conducted an integrative critical review of caloric restriction (CR), intermittent fasting (IF), and caloric restriction mimetics (CR-mimetics) to compare shared mechanisms, clinical evidence, limitations, and translational potential. Across modalities, CR and IF consistently activate AMP-activated protein kinase and sirtuins, inhibit mTOR (mechanistic target of rapamycin) signaling, and enhance autophagy, aligning with improvements in insulin sensitivity, lipid profile, low-grade inflammation, and selected epigenetic aging measures in humans. CR-mimetics, such as metformin, resveratrol, rapamycin, and spermidine, partially reproduce these effects; however, long-term safety and efficacy in healthy populations remain incompletely defined. Methodological constraints—short trial duration, selective samples, intermediate (nonclinical) endpoints, and limited adherence monitoring—impede definitive conclusions on hard outcomes (frailty, disability, hospitalization, mortality). We propose the Active Management of Aging and Longevity (AMAL) model, a three-level biomarker-guided framework that integrates personalized diet, chrono-nutrition, exercise, and the selective use of CR-mimetics, along with digital monitoring and decision support. AMAL emphasizes epigenetic clocks, multi-omics profiling, inflammatory and microbiome metrics, and adaptive protocols to enhance adherence and clinical relevance. Overall, CR, IF, and CR mimetics constitute promising, complementary strategies to modulate biological aging; rigorous long-term trials with standardized biomarkers and clinically meaningful endpoints are needed to enable their scalable implementation. Full article
(This article belongs to the Special Issue The Roles of Diet and Nutrition in Metabolic Diseases: Advancements in Molecular Insights)
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