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Insights from Genetics, Epigenetics, and Microbiome Research in Obesity: Integrative Approaches to Understand Metabolic Disorders

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Bioinformatics and Systems Biology".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 3968

Special Issue Editor

Dr. Shengping Yang

E-Mail Website
Guest Editor
Pennington Biomedical Research Center, Baton Rouge, LA, USA
Interests: statistical methodologies; genomics

Special Issue Information

Dear Colleagues,

The obesity epidemic poses a significant global health challenge, impacting numerous aspects of metabolic health and quality of life. While traditional approaches have emphasized lifestyle factors, such as diet and exercise, recent research has increasingly highlighted the intricate roles of genetics, epigenetics, and the microbiome in shaping obesity risk and progression. However, research in these areas presents significant challenges. The complexity of genetic influence, the dynamic nature of epigenetic modifications, and the highly variable composition of the microbiome all make it difficult to establish clear causal relationships and develop effective interventions. Additionally, integrating data from these diverse fields requires sophisticated computational tools and large, well-designed studies. Despite these challenges, by focusing on the critical areas of genetics, epigenetics, and the microbiome, this Special Issue aims to advance our understanding of the complex nature of obesity and contribute to the development of more effective prevention and treatment strategies. Research applying the state-of-the-art artificial intelligence concepts is highly encouraged.

Dr. Shengping Yang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Issues in Molecular Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • obesity
  • epigenetics
  • microbiom
  • genetics
  • bioinformatics

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Published Papers (4 papers)

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Research

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11 pages, 253 KB  
Article
Association of Nrf2 Single Nucleotide Polymorphism rs35652124 and FABP4 Levels with Peripheral Artery Disease Among Type 2 Diabetes Mellitus Pakistani Population
by Iqra Ayaz, Nakhshab Choudhry, Amna Ihsan, Tehreem Zubair, Aamir Jamal Gondal and Nighat Yasmin
Curr. Issues Mol. Biol. 2025, 47(7), 530; https://doi.org/10.3390/cimb47070530 - 9 Jul 2025
Viewed by 330
Abstract
Peripheral arterial disease (PAD) is a macrovascular diabetic complication, characterized by atherosclerotic plaque formation due to hyperglycemia and dyslipidemia. The molecular mechanisms involved in PAD-T2DM pathogenesis will help in understanding and early prognosis; therefore, we aim to evaluate FABP4 levels and Nrf2 single-nucleotide [...] Read more.
Peripheral arterial disease (PAD) is a macrovascular diabetic complication, characterized by atherosclerotic plaque formation due to hyperglycemia and dyslipidemia. The molecular mechanisms involved in PAD-T2DM pathogenesis will help in understanding and early prognosis; therefore, we aim to evaluate FABP4 levels and Nrf2 single-nucleotide polymorphisms (SNPs) among PAD-T2DM patients. In a case-control study, 123 samples (healthy control HC, T2DM, and PAD-T2DM; n = 41 each) were collected from the diabetic foot clinic at Mayo Hospital, Lahore. Baseline and biochemical data were collected. PAD diagnosis was established by measuring the ankle-brachial index with color Doppler ultrasound. Serum FABP4 levels were measured using an ELISA. Nrf2 SNP rs35652124 analysis was performed by restriction fragment length polymorphism. PAD-T2DM prevalence was higher among male subjects (61.1%). Fasting plasma glucose levels (p = 0.02), total cholesterol (p < 0.0001), and LDL-cholesterol (p = 0.01) were significantly higher in PAD-T2DM as compared to T2DM. SNP association analysis showed that homozygous genotype TT (OR: 3.85, 95% (CI): 1.22–12.11, p = 0.02) and T-allele (OR: 1.31, 95% (CI): 1.31–4.67, p = 0.005) were significantly associated with PAD-T2DM. FABP4 levels were higher in the PAD-T2DM group as compared to T2DM (p < 0.0001) and were significantly associated with Nrf2 SNP genotype TT (p < 0.001) and CT (p = 0.01) in PAD-T2DM. Our results showed, for the first time, that the Nrf2 SNP is significantly associated with PAD-T2DM and FABP4 levels compared to T2DM. Full article
(This article belongs to the Special Issue Insights from Genetics, Epigenetics, and Microbiome Research in Obesity: Integrative Approaches to Understand Metabolic Disorders)

Review

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23 pages, 864 KB  
Review
Physiological Mechanisms of and Therapeutic Approaches to the Gut Microbiome and Low-Grade Inflammation in Obesity
by Agnieszka Pelc, Weronika Fic, Tymoteusz Typrowicz and Ewelina Polak-Szczybyło
Curr. Issues Mol. Biol. 2025, 47(8), 637; https://doi.org/10.3390/cimb47080637 - 8 Aug 2025
Viewed by 672
Abstract
Obesity is a growing global health challenge, closely linked to chronic low-grade inflammation. This persistent, low-intensity immune response contributes to the development of metabolic, cardiovascular, and cancer-related diseases. A key player in this process is the gut microbiota. Dysbiosis, an imbalance in gut [...] Read more.
Obesity is a growing global health challenge, closely linked to chronic low-grade inflammation. This persistent, low-intensity immune response contributes to the development of metabolic, cardiovascular, and cancer-related diseases. A key player in this process is the gut microbiota. Dysbiosis, an imbalance in gut bacterial composition, disrupts metabolic function, weakens the intestinal barrier, and promotes the production of pro-inflammatory cytokines. In people with obesity, gut microbial diversity is reduced, and the ratio of beneficial to harmful bacteria shifts, affecting lipid metabolism and immune balance. Short-chain fatty acids, produced by gut bacteria, help maintain gut integrity and reduce inflammation. Butyrate, a major SCFA, also improves insulin sensitivity and may support obesity treatment. Diet plays a central role in shaping the gut microbiome. Western diets tend to promote dysbiosis and inflammation, while Mediterranean-style diets encourage the growth of beneficial bacteria. Targeted modulation of the microbiota through diet, probiotics, or medication emerges as a promising strategy for preventing and managing obesity. Full article
(This article belongs to the Special Issue Insights from Genetics, Epigenetics, and Microbiome Research in Obesity: Integrative Approaches to Understand Metabolic Disorders)
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18 pages, 1491 KB  
Review
Effects of Aerobic Exercise on Sleep Quality, Insomnia, and Inflammatory Markers: A Systematic Review and Meta-Analysis
by Mariazel Rubio-Valles and Arnulfo Ramos-Jimenez
Curr. Issues Mol. Biol. 2025, 47(7), 572; https://doi.org/10.3390/cimb47070572 - 20 Jul 2025
Viewed by 1452
Abstract
Poor sleep quality and insomnia are increasingly linked to chronic inflammation and obesity-related metabolic dysfunction. Aerobic exercise is a promising non-pharmacological approach for enhancing sleep quality and reducing systemic inflammation; Therefore, we aim to systematically evaluate and quantify the effects of aerobic exercise [...] Read more.
Poor sleep quality and insomnia are increasingly linked to chronic inflammation and obesity-related metabolic dysfunction. Aerobic exercise is a promising non-pharmacological approach for enhancing sleep quality and reducing systemic inflammation; Therefore, we aim to systematically evaluate and quantify the effects of aerobic exercise interventions on subjective sleep quality, insomnia severity, and circulating markers (IL-6 and TNF-α) in adults. A systematic search was conducted in institutional databases (UNAM, UACJ) and PubMed to identify randomized controlled trials (RCTs) examining the effects of exercise on sleep and inflammation. Risk of bias was assessed using the Cochrane RoB2 tool. Meta-analyses were performed using RevMan 5.4 with random-effects models to estimate pooled mean differences (MD) and standardized mean differences (SMD), with 95% confidence intervals. Anaerobic protocols were excluded from the meta-analysis due to the insufficient availability of data. : Eleven RCTs met the inclusion criteria. Aerobic exercise showed a significant pooled effect on sleep outcomes (MD = −2.51; 95% CI: −4.80 to −0.23; p = 0.03). However, subgroup analyses for Pittsburgh Sleep Quality Index (PSQI) (MD = −2.27; p = 0.15) and Insomnia Severity Index (ISI) (MD = −2.98; p = 0.16) were not statistically significant. Two studies on IL-6 reported a non-significant reduction (SMD = −0.17; p = 0.66), with moderate heterogeneity. TNF-α results were also non-significant (SMD = 0.60; p = 0.29) with substantial variability. Our results showed that aerobic exercise may modestly improve sleep outcomes; however, current evidence does not support its effectiveness in reducing levels of IL-6 or TNF-α. Further well-controlled trials are needed to clarify its immunometabolic effects, particularly in populations with obesity or metabolic disorders. Full article
(This article belongs to the Special Issue Insights from Genetics, Epigenetics, and Microbiome Research in Obesity: Integrative Approaches to Understand Metabolic Disorders)
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17 pages, 6230 KB  
Review
Gut–Adipose Tissue Axis and Metabolic Health
by Sanja Borozan, Cornelius J. Fernandez, Adnan Samee and Joseph M. Pappachan
Curr. Issues Mol. Biol. 2025, 47(6), 424; https://doi.org/10.3390/cimb47060424 - 6 Jun 2025
Viewed by 941
Abstract
The gut–adipose tissue axis plays a crucial role in metabolic health. It is a two-way communication pathway between the gastrointestinal tract and adipose tissue. This axis influences physiological processes vital for maintaining metabolic health, including energy homeostasis, lipid metabolism, and inflammation. Emerging research [...] Read more.
The gut–adipose tissue axis plays a crucial role in metabolic health. It is a two-way communication pathway between the gastrointestinal tract and adipose tissue. This axis influences physiological processes vital for maintaining metabolic health, including energy homeostasis, lipid metabolism, and inflammation. Emerging research suggests that the gut microbiota, composed of trillions of microorganisms residing in the intestines, significantly impacts this axis by modulating host metabolism. An imbalance in the gut microbiota (dysbiosis) has been linked to obesity, insulin resistance, and other metabolic disorders. Innovative therapeutic strategies and dietary interventions aimed at modulating the gut–adipose tissue axis have shown encouraging results in improving metabolic health. A deeper critical understanding of the gut–adipose tissue axis is, therefore, essential in understanding the pathophysiology of metabolic disorders so that targeted interventions can be developed to prevent and treat these metabolic disorders. This article highlights the need for integrative approaches that consider both gastrointestinal and adipose functions in metabolic health management. Full article
(This article belongs to the Special Issue Insights from Genetics, Epigenetics, and Microbiome Research in Obesity: Integrative Approaches to Understand Metabolic Disorders)
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