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Metabolic Syndrome: New Insights in Pathogenesis, Diagnosis, Prevention, and Management
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Metabolic Syndrome: New Insights in Pathogenesis, Diagnosis, Prevention, and Management

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: 20 September 2025 | Viewed by 7531

Special Issue Editors

Prof. Dr. Lucia Maria Procopciuc

E-Mail Website
Guest Editor
Medical Biochemistry Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
Interests: genetics; epigenetics; medical biochemistry; metabolic disorders
Prof. Dr. Roxana Liana Lucaciu

E-Mail Website
Guest Editor
Pharmaceutical Biochemistry and Clinical Laboratory Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
Interests: (clinical) biochemistry; medicinal chemistry; drug discovery; anticancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolic syndrome (syndrome X, insulin resistance syndrome) is a multifactorial disease, with higher morbidity and mortality risk and increased frequency in younger people. It includes a cluster of risk factors for cardiovascular diseases caused by adipose tissue dysfunction and insulin resistance. Risk factors most closely tied to metabolic syndrome include age, ethnicity, a body mass index greater than 25, a personal or family history of diabetes, smoking, stress, being post-menopause, high-fat diet, a sedentary lifestyle, and hormonal imbalance. Genetic factors could influence each individual component of the syndrome and the syndrome itself. The genetic components of hypertension, obesity, dyslipidemia, oxidative stress, inflammation, cytokine hypersecretion, and epigenetic modifications should also be considered in metabolic syndrome risk factors.

According to the National Heart, Lung, and Blood Institute (NHLBI), and the American Heart Association (AHA), metabolic syndrome is diagnosed when a patient has at least three of the following five conditions: abdominal obesity, hypertension, hyperglycemia, hypertriglyceridemia, and a lower HDL-cholesterol level.

Metabolic syndrome greatly raises the risk of developing coronary heart disease, stroke, diabetes, fatty liver, polycystic ovarian syndrome, cholesterol gallstones, asthma, sleep problems, and several types of cancer.

This Special Issue will include original research, case reports, and review papers investigating the biochemical, genetic, and epigenetic biomarkers related to the risk of developing metabolic syndrome in order to elucidate the pathogenic mechanism. Furthermore, this Special Issue will consider in silico, experimental in vitro, and in vivo studies with higher potential to improve the management (prevention, diagnosis, and treatment) of metabolic syndrome.

Prof. Dr. Lucia Maria Procopciuc
Prof. Dr. Roxana Liana Lucaciu
Guest Editors

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • insulin resistance
  • hypertension
  • diabetes mellitus
  • obesity
  • inflammation
  • stress
  • metabolic disorders
  • reproductive endocrine disorders
  • polycystic ovarian syndrome
  • waist circumference
  • estrogen deficiency
  • disturbances in adipose tissue
  • physical inactivity
  • overnutrition
  • cardiovascular diseases
  • abdominal obesity
  • genetics and epigenetics of metabolic syndrome
  • computational analysis

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Published Papers (6 papers)

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Research

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32 pages, 4993 KiB  
Article
Loosening the Lid on Shoulder Osteoarthritis: How the Transcriptome and Metabolic Syndrome Correlate with End-Stage Disease
by Samuel J. Lynskey, Zihui Ling, Mark Ziemann, Stephen D. Gill, Sean L. McGee and Richard S. Page
Int. J. Mol. Sci. 2025, 26(7), 3145; https://doi.org/10.3390/ijms26073145 (registering DOI) - 28 Mar 2025
Viewed by 206
Abstract
Metabolic syndrome (MetS) associated with Osteoarthritis (OA) is an increasingly recognised entity. Whilst the degenerative pattern in cuff-tear arthropathy (CTA) has been well documented, the biological processes behind primary shoulder OA and CTA remain less understood. This study investigates transcriptomic differences in these [...] Read more.
Metabolic syndrome (MetS) associated with Osteoarthritis (OA) is an increasingly recognised entity. Whilst the degenerative pattern in cuff-tear arthropathy (CTA) has been well documented, the biological processes behind primary shoulder OA and CTA remain less understood. This study investigates transcriptomic differences in these conditions, alongside the impact of MetS in patients undergoing total shoulder replacement. In a multi-centre study, 20 OA patients undergoing total shoulder replacement were included based on specific treatment indications for OA and cuff-tear arthropathy as well as 25 patients undergoing rotator cuff repair (RCR) as a comparator group. Tissues from subchondral bone, capsule (OA and RCR), and synovium were biopsied, and RNA sequencing was performed using Illumina platforms. Differential gene expression was conducted using DESeq2, adjusting for demographic factors, followed by pathway enrichment using the mitch package. Gene expressions in CTA and primary OA was differentially affected. CTA showed mitochondrial dysfunction, GATD3A downregulation, and increased cartilage degradation, while primary OA was marked by upregulated inflammatory and catabolic pathways. The effect of MetS on these pathologies was further shown. MetS further disrupted WNT/β-catenin signalling in CTA, and in OA. Genes such as ACAN, PANX3, CLU, and VAT1L were upregulated, highlighting potential biomarkers for early OA detection. This transcriptomic analysis reveals key differences between end-stage CTA and primary glenohumeral OA. CTA shows heightened metabolic/protein synthesis activity with less immune-driven inflammation. Under MetS, mitochondrial dysfunction (including GATD3A downregulation) and altered Wnt/β-catenin signalling intensify cartilage and bone damage. In contrast, primary OA features strong complement activation, inflammatory gene expression, and collagen remodelling. MetS worsens both conditions via oxidative stress, advanced glycation end products, and ECM disruption—particularly, increased CS/DS degradation. These distinctions support targeted treatments, from antioxidants and Wnt modulators to aggrecanase inhibitors or clusterin augmentation. Addressing specific molecular disruptions, especially those amplified by MetS, may preserve shoulder function, delay surgical intervention, and improve long-term patient outcomes. Full article
(This article belongs to the Special Issue Metabolic Syndrome: New Insights in Pathogenesis, Diagnosis, Prevention, and Management)
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11 pages, 1150 KiB  
Article
Distribution and Characteristics of Oral Pathogens According to Blood Glucose Levels in South Korean Health Examinees
by Yong Jun Choi, Jooheon Park, Myung Geun Shin, Bong-Kwang Jung, Hyejoo Shin, Seon Cho, Han-Ik Cho and Eun-Hee Nah
Int. J. Mol. Sci. 2025, 26(6), 2638; https://doi.org/10.3390/ijms26062638 - 14 Mar 2025
Viewed by 144
Abstract
The distribution of oral pathogens is influenced by genetic background, diet, socioeconomic status, and racial factors. This study aimed to assess the distribution and characteristics of oral pathogens based on blood glucose levels in a South Korean population. This cross-sectional, retrospective study included [...] Read more.
The distribution of oral pathogens is influenced by genetic background, diet, socioeconomic status, and racial factors. This study aimed to assess the distribution and characteristics of oral pathogens based on blood glucose levels in a South Korean population. This cross-sectional, retrospective study included subjects from 17 health promotion centers in 13 South Korean cities between November 2021 and December 2022. Real-time multiplex PCR was used to detect 10 periodontitis-related pathogens, 6 dental caries-related pathogens, and 1 dental caries-protective bacterium. The most prevalent periodontitis-related pathogens were Parvimonas micra (97.6%), Porphyromonas endodontalis (96.8%), and Treponema socranskii (95.0%). Among dental caries-related pathogens, Streptococcus sanguinis and Veillonella parvula were found in all subjects. The prevalence of periodontitis-related pathogens was higher in males, while pathogens related to periodontitis and dental caries were more prevalent in older individuals. In the diabetes group, Aggregatibacter actinomycetemcomitans, red and orange complexes, and Streptococcus mutans were more prevalent. The relative amount of S. sanguinis was lower, while V. parvula was higher in individuals with diabetes mellitus. The prevalence and composition of oral pathogens vary by sex, age, and blood glucose levels. Diabetic individuals showed a pathogenic community structure linked to increased risks of periodontitis and dental caries. Full article
(This article belongs to the Special Issue Metabolic Syndrome: New Insights in Pathogenesis, Diagnosis, Prevention, and Management)
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19 pages, 3882 KiB  
Article
The Effect of Pomegranate Peel Extract on the Oxidative and Inflammatory Status in the Spleens of Rats with Metabolic Syndrome
by Alina Rak-Pasikowska, Kornela Hałucha, Marta Kamińska, Joanna Niewiadomska, Agnieszka Noszczyk-Nowak and Iwona Bil-Lula
Int. J. Mol. Sci. 2024, 25(22), 12253; https://doi.org/10.3390/ijms252212253 - 14 Nov 2024
Viewed by 1302
Abstract
Polyphenols have antioxidant and anti-inflammatory properties and maintain the immune system in balance; therefore, the aim of the study was to investigate the effect of polyphenols present in pomegranate peel extract on the spleens of rats with metabolic syndrome. The study objects were [...] Read more.
Polyphenols have antioxidant and anti-inflammatory properties and maintain the immune system in balance; therefore, the aim of the study was to investigate the effect of polyphenols present in pomegranate peel extract on the spleens of rats with metabolic syndrome. The study objects were adult male Zucker Diabetic Fatty (ZDF-Leprfa/Crl, fa/fa) rats. The rats were divided into a control group (MetS) consisting of rats with metabolic syndrome and four study groups consisting of rats with metabolic syndrome (MetS + 100 mg and MetS + 200 mg) or healthy animals (H + 100 mg and H + 200 mg) receiving polyphenol extract at a dose of 100 mg or 200 mg/kg, respectively. Concentrations of IL-6, NF-κB, NFATc1, Cyt-C, TNFα, MMP-2, ROS/RNS, and MDA were measured; the activities of GPX, SOD, CAT, MMP-2, and MMP-9 were assessed; and the expression of the BAX and BCL-2 genes was evaluated in homogenized spleens. In conclusion, pomegranate extract may lead to an increase in catalase and glutathione peroxidase activity. Additionally, it may have a reducing effect on the ROS/RNS level, leading to a reduction in the activity of SOD in the MetS groups with PPE administration. Moreover, the BCL-2 gene showed lower expression in the MetS + 100 mg group compared to the H + 100 mg group, indicating that the balance between pro- and antiapoptotic factors of the BCL-2 family may be disrupted by the metabolic syndrome promoting the proapoptotic pathway. Full article
(This article belongs to the Special Issue Metabolic Syndrome: New Insights in Pathogenesis, Diagnosis, Prevention, and Management)
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18 pages, 2644 KiB  
Article
Metabolic Syndrome, Inflammation, Oxidative Stress, and Vitamin D Levels in Children and Adolescents with Obesity
by Tjaša Hertiš Petek, Evgenija Homšak, Mateja Svetej and Nataša Marčun Varda
Int. J. Mol. Sci. 2024, 25(19), 10599; https://doi.org/10.3390/ijms251910599 - 1 Oct 2024
Cited by 4 | Viewed by 1388
Abstract
Metabolic syndrome (MetS) is associated with systemic inflammation, oxidative stress, and hypovitaminosis D. Our aim was to determine whether vitamin D mediates inflammation and oxidative stress, assessed through selected biomarkers, in children with obesity and/or MetS. Eighty children with normal weight, overweight, or [...] Read more.
Metabolic syndrome (MetS) is associated with systemic inflammation, oxidative stress, and hypovitaminosis D. Our aim was to determine whether vitamin D mediates inflammation and oxidative stress, assessed through selected biomarkers, in children with obesity and/or MetS. Eighty children with normal weight, overweight, or obesity were analyzed for serum vitamin D, C-reactive protein, leukocytes, adiponectin, monocyte chemoattractant protein-1, myeloperoxidase, interferon-inducible T-cell alpha chemoattractant (I-TAC/CXCL11), superoxide dismutase-1, fasting lipid and glucose levels, ultrasound-measured abdominal fat thickness, waist circumference, body mass index and blood pressure. Children with obesity or overweight had lower vitamin D levels, increased blood pressure, visceral and subcutaneous fat thickness, and higher leukocytes, C-reactive protein, and myeloperoxidase levels. Those with MetS also had lower adiponectin levels. Vitamin D levels are negatively correlated with body mass index, waist circumference, and visceral and subcutaneous fat thickness. Correlation, mediation, and regression analyses showed no link between vitamin D and inflammatory/oxidative stress variables. The novel biomarker I-TAC did not correlate with obesity or vitamin D status. Our results indicate that vitamin D does not significantly mediate inflammation or oxidative stress in children and adolescents with obesity and/or MetS. Selected inflammation/oxidative stress biomarkers appear to be altered primarily due to obesity rather than vitamin D status. Full article
(This article belongs to the Special Issue Metabolic Syndrome: New Insights in Pathogenesis, Diagnosis, Prevention, and Management)
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10 pages, 1745 KiB  
Review
Increased Leptin Levels in Plasma and Serum in Patients with Metabolic Disorders: A Systematic Review and Meta-Analysis
by Yazmín Hernández-Díaz, María de los Ángeles Ovando-Almeida, Ana Fresán, Isela Esther Juárez-Rojop, Alma Delia Genis-Mendoza, Humberto Nicolini, Thelma Beatriz González-Castro, Carlos Alfonso Tovilla-Zárate and María Lilia López-Narváez
Int. J. Mol. Sci. 2024, 25(23), 12668; https://doi.org/10.3390/ijms252312668 - 26 Nov 2024
Viewed by 901
Abstract
A large number of studies have reported the relationships between leptin levels and diabetes or obesity. However, the results are still controversial, and no consensus has been reached. Therefore, the purpose of the study was to collect data from various databases to perform [...] Read more.
A large number of studies have reported the relationships between leptin levels and diabetes or obesity. However, the results are still controversial, and no consensus has been reached. Therefore, the purpose of the study was to collect data from various databases to perform a meta-analysis and address the inconsistencies in these studies. A systematic literature search was conducted on PubMed, Web of Science, and EBSCO for relevant available articles. The pooled standard mean difference (SMD) with 95% confidence interval (CI) was used to estimate the association by a meta-analysis. Fifteen reports with 1,388 cases and 3,536 controls were chosen for the meta-analysis. First, an increase in leptin levels in serum (SMD 0.69; 95% CI 0.36–1.02 ng/mL) and plasma (SMD 0.46; 95% CI 0.18–0.74 ng/mL) was observed in individuals with diabetes compared to controls. This increased level was also observed by gender and population. Second, statistical analysis showed that leptin levels in serum were significantly increased in individuals with obesity (SMD 1.03; 95% CI 0.72–1.34 ng/mL). This meta-analysis analyzed leptin in individuals with diabetes or obesity and emphasized the importance of monitoring serum/plasma leptin levels in patients with these diseases. However, more comprehensive studies are necessary in order to draw firm conclusions. Full article
(This article belongs to the Special Issue Metabolic Syndrome: New Insights in Pathogenesis, Diagnosis, Prevention, and Management)
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21 pages, 796 KiB  
Review
Maternal Dietary Strategies for Improving Offspring Cardiovascular–Kidney–Metabolic Health: A Scoping Review
by You-Lin Tain and Chien-Ning Hsu
Int. J. Mol. Sci. 2024, 25(18), 9788; https://doi.org/10.3390/ijms25189788 - 10 Sep 2024
Cited by 2 | Viewed by 2220
Abstract
Dietary regulation has been recognized for its profound impact on human health. The convergence of cardiovascular, kidney, and metabolic disorders at the pathophysiological level has given rise to cardiovascular–kidney–metabolic (CKM) syndrome, which constitutes a significant global health burden. Maternal dietary nutrients play a [...] Read more.
Dietary regulation has been recognized for its profound impact on human health. The convergence of cardiovascular, kidney, and metabolic disorders at the pathophysiological level has given rise to cardiovascular–kidney–metabolic (CKM) syndrome, which constitutes a significant global health burden. Maternal dietary nutrients play a crucial role in fetal development, influencing various programmed processes. This review emphasizes the effects of different types of dietary interventions on each component of CKM syndrome in both preclinical and clinical settings. We also provide an overview of potential maternal dietary strategies, including amino acid supplementation, lipid-associated diets, micronutrients, gut microbiota-targeted diets, and plant polyphenols, aimed at preventing CKM syndrome in offspring. Additionally, we discuss the mechanisms mediated by nutrient-sensing signals that contribute to CKM programming. Altogether, we underscore the interaction between maternal dietary interventions and the risk of CKM syndrome in offspring, emphasizing the need for continued research to facilitate their clinical translation. Full article
(This article belongs to the Special Issue Metabolic Syndrome: New Insights in Pathogenesis, Diagnosis, Prevention, and Management)
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