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Genetic and Molecular Mechanisms of Obesity
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Genetic and Molecular Mechanisms of Obesity

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: 30 December 2025 | Viewed by 1931

Special Issue Editors

Prof. Dr. Maria Elisabeth Street

E-Mail Website
Guest Editor
Pediatric Unit, Department of Medicine and Surgery, University of Parma, Via Gramsci, 14, 43124 Parma, Italy
Interests: growth; GH; IGF system; inflammation; insulin resistance; obesity; PCOS; miRNAs; endocrine disruptors
Special Issues, Collections and Topics in MDPI journals
Dr. Giuseppina Rosaria Umano

E-Mail Website
Guest Editor
Department of the Woman, the Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
Interests: fobesity; genetics; NAFLD; OSAS

Special Issue Information

Dear Colleagues,

Globally, the prevalence of obesity is rising, impacting 159 million children and adolescents and 879 million adults. The risk of cardiovascular diseases (including hypertension, stroke, and heart attacks), autoimmune diseases, some types of cancer, insulin resistance, diabetes, and other comorbidities is increased in those with excess body fat already in childhood. Despite the significant health and economic costs associated with obesity, the molecular mechanisms underpinning its etiology are still poorly understood. The role of the genetic background has been described in the past as a key player in the regulation of the balance between caloric intake and energy expenditure. However, a rising number of new genetic variants and polymorphisms continue to be reported in association with obesity risk. The regulation of adipogenesis by long non-coding RNAs, oxidative stress brought on by pro-inflammatory adipokines released by adipose tissue, epigenetic modifications, and alterations in the gut microbiome that result in disturbed glucose and lipid homeostasis and satiety signaling are among the mechanisms linked to obesity. The aim of this Special Issue is to collect original and review articles to provide the most updated molecular knowledge in the field of obesity.

Prof. Dr. Maria Elisabeth Street
Dr. Giuseppina Rosaria Umano
Guest Editors

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. 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

  • obesity
  • insulin signal transduction
  • insulin sensitivity
  • co-morbidities
  • genetics
  • epigenetics
  • miRNAs
  • DNA methylation
  • molecular mechanisms

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Published Papers (2 papers)

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Research

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11 pages, 275 KiB  
Article
Polygenic Score for Body Mass Index Is Associated with Weight Loss and Lipid Outcomes After Metabolic and Bariatric Surgery
by Luana Aldegheri, Chiara Cipullo, Natalia Rosso, Eulalia Catamo, Biagio Casagranda, Pablo Giraudi, Nicolò de Manzini, Silvia Palmisano and Antonietta Robino
Int. J. Mol. Sci. 2025, 26(15), 7337; https://doi.org/10.3390/ijms26157337 - 29 Jul 2025
Viewed by 227
Abstract
Metabolic and bariatric surgery (MBS) is an effective treatment for severe obesity, though individual responses vary widely, partly due to genetic predisposition. This study investigates the association of a body mass index (BMI) polygenic score (PGS) with weight loss and metabolic outcomes following [...] Read more.
Metabolic and bariatric surgery (MBS) is an effective treatment for severe obesity, though individual responses vary widely, partly due to genetic predisposition. This study investigates the association of a body mass index (BMI) polygenic score (PGS) with weight loss and metabolic outcomes following surgery. A cohort of 225 patients undergoing MBS was analyzed at baseline (T0), six (T6), and twelve (T12) months, with anthropometric and biochemical parameters recorded at each time point. Total weight loss (TWL) and excess weight loss (EWL) percentages were calculated. PGS was computed using the LDpred-grid Bayesian method. The mean age was 45.9 ± 9.4 years. Males had a higher baseline prevalence of type 2 diabetes (T2D) and comorbidities (p < 0.001). Linear regression analysis confirmed an association between PGS and baseline BMI (p = 0.012). Moreover, mediation analysis revealed that baseline BMI mediated the effect of the PGS on %TWL at T12, with an indirect effect (p-value = 0.018). In contrast, high-density lipoprotein-cholesterol (HDL-C) at T6 and triglycerides (TG) at T12 showed direct associations with the PGS (p-value = 0.004 and p-value = 0.08, respectively), with no significant mediation by BMI. This study showed a BMI-mediated association of PGS with %TWL and a direct association with lipid changes, suggesting its potential integration into personalized obesity treatment. Full article
(This article belongs to the Special Issue Genetic and Molecular Mechanisms of Obesity)

Review

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41 pages, 1640 KiB  
Review
Early Roots of Childhood Obesity: Risk Factors, Mechanisms, and Prevention Strategies
by Giuseppina Rosaria Umano, Simonetta Bellone, Raffaele Buganza, Valeria Calcaterra, Domenico Corica, Luisa De Sanctis, Anna Di Sessa, Maria Felicia Faienza, Nicola Improda, Maria Rosaria Licenziati, Melania Manco, Carla Ungaro, Flavia Urbano, Giuliana Valerio, Malgorzata Wasniewska and Maria Elisabeth Street
Int. J. Mol. Sci. 2025, 26(15), 7388; https://doi.org/10.3390/ijms26157388 - 30 Jul 2025
Viewed by 434
Abstract
Childhood obesity is a growing global health concern, with established links to physical activity, nutrition, and, increasingly, to prenatal and perinatal factors. Emerging evidence highlights the significant role of maternal conditions such as obesity, comorbidities, nutrition, and environmental exposures in predisposing offspring to [...] Read more.
Childhood obesity is a growing global health concern, with established links to physical activity, nutrition, and, increasingly, to prenatal and perinatal factors. Emerging evidence highlights the significant role of maternal conditions such as obesity, comorbidities, nutrition, and environmental exposures in predisposing offspring to long-term metabolic and cardiovascular diseases. The “Developmental Origins of Health and Disease” (DOHaD) paradigm provides a framework for understanding how early life environmental exposures, particularly during the periconceptional, fetal, and neonatal periods, can program future health outcomes through epigenetic mechanisms. Epigenetic modifications alter gene expression without changing the DNA sequence and are increasingly recognized as key mediators in the development of obesity. This narrative review summarizes current findings on the early determinants of childhood obesity, emphasizing the molecular and epigenetic pathways involved. A comprehensive literature search was conducted across multiple databases and international sources, focusing on recent studies from the past decade. Both human and animal research were included to provide a broad perspective. This review aims to consolidate recent insights into early life influences on obesity, underscoring the need for preventive strategies starting as early as the preconception period. Full article
(This article belongs to the Special Issue Genetic and Molecular Mechanisms of Obesity)
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