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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Preliminary Study on Circulating REG3α and Its Associations with Vitamin D Supplementation and Inflammatory Biomarkers in Adults with Overweight and Obesity

by
Theocharis Koufakis
1,*,
Dimitrios Kouroupis
1,
Areti Kourti
2,
Paraskevi Karalazou
2,
Katerina Thisiadou
2,
Ioannis Georgiadis
3,
Omar Mustafa
4,5,
Giuseppe Maltese
6,7,
Luca Busetto
8,
Djordje S. Popovic
9,
Olga Giouleme
1,
Kalliopi Kotsa
10,
Michael Doumas
1 and
Kali Makedou
2
1
Second Propaedeutic Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, Greece
2
Laboratory of Biochemistry, School of Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, 54124 Thessaloniki, Greece
3
National Primary Health Care Network, 61200 Polykastron, Greece
4
Department of Diabetes, King’s College Hospital NHS Foundation Trust, SE5 9RS London, UK
5
King’s College, WC2R 2LS London, UK
6
Department of Diabetes and Endocrinology, Epsom & St Helier University Hospitals, KT18 7EG Epsom, UK
7
Unit for Metabolic Medicine, Cardiovascular Division, Faculty of Life Sciences & Medicine, King’s College, WC2R 2LS London, UK
8
Department of Medicine, University of Padova, 35122 Padova, Italy
9
Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre of Vojvodina, Medical Faculty, University of Novi Sad, 21000 Novi Sad, Serbia
10
Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece
*
Author to whom correspondence should be addressed.
Curr. Issues Mol. Biol. 2025, 47(12), 970; https://doi.org/10.3390/cimb47120970
Submission received: 21 October 2025 / Revised: 17 November 2025 / Accepted: 21 November 2025 / Published: 21 November 2025
(This article belongs to the Special Issue Molecular Mechanisms of Gut Microbiota in Health, Immunity and Disease)
Versions Notes

Abstract

Objective: Obesity is characterized by chronic inflammation and gut dysbiosis, yet circulating markers reflecting intestinal immune activation remain limited. Regenerating islet-derived protein 3 alpha (REG3α), an antimicrobial peptide secreted by intestinal Paneth cells, plays a pivotal role in mucosal defense and mirrors microbial–epithelial interactions. In this cross-sectional study, we aimed to examine circulating REG3α levels in infection-free adults with obesity, overweight, and normal weight, and to explore their associations with vitamin D supplementation and biomarkers of inflammation and dysbiosis. Methods: Sixty-nine participants were stratified into control, overweight, and obesity groups. Serum REG3α, interleukin-6 (IL-6), β-defensin-2, high-sensitivity c-reactive protein, ferritin, and presepsin were assessed. Vitamin D status and supplementation history were recorded. Multivariable linear regression, principal component analysis (PCA), and bootstrap mediation models were applied to explore associations and potential indirect effects. Results: REG3α concentrations were higher in overweight and obesity compared to controls (646 ± 217 vs. 521 ± 311 ng/mL); however, the difference was not significant (p = 0.15). Vitamin D supplementation was inversely associated with REG3α (p = 0.06), and this effect appeared weaker in obesity. REG3α correlated positively with IL-6 (ρ = 0.28) and β-defensin-2 (ρ = 0.43). PCA revealed a shared inflammatory–mucosal activation component that predicted REG3α levels. Exploratory mediation suggested a partial indirect effect of vitamin D via reduced inflammatory activity. Conclusions: Circulating REG3α shows associations with indicators of inflammation and vitamin D supplementation in individuals with overweight and obesity. Although differences between groups did not reach statistical significance, the observed trends suggest possible links between mucosal immune activity and metabolic status. These exploratory results warrant validation in larger, longitudinal studies before any biomarker role can be established.
Keywords: REG3α; obesity; vitamin D; inflammation; gut dysbiosis; antimicrobial peptides; mucosal immunity REG3α; obesity; vitamin D; inflammation; gut dysbiosis; antimicrobial peptides; mucosal immunity

Share and Cite

MDPI and ACS Style

Koufakis, T.; Kouroupis, D.; Kourti, A.; Karalazou, P.; Thisiadou, K.; Georgiadis, I.; Mustafa, O.; Maltese, G.; Busetto, L.; Popovic, D.S.; et al. Preliminary Study on Circulating REG3α and Its Associations with Vitamin D Supplementation and Inflammatory Biomarkers in Adults with Overweight and Obesity. Curr. Issues Mol. Biol. 2025, 47, 970. https://doi.org/10.3390/cimb47120970

AMA Style

Koufakis T, Kouroupis D, Kourti A, Karalazou P, Thisiadou K, Georgiadis I, Mustafa O, Maltese G, Busetto L, Popovic DS, et al. Preliminary Study on Circulating REG3α and Its Associations with Vitamin D Supplementation and Inflammatory Biomarkers in Adults with Overweight and Obesity. Current Issues in Molecular Biology. 2025; 47(12):970. https://doi.org/10.3390/cimb47120970

Chicago/Turabian Style

Koufakis, Theocharis, Dimitrios Kouroupis, Areti Kourti, Paraskevi Karalazou, Katerina Thisiadou, Ioannis Georgiadis, Omar Mustafa, Giuseppe Maltese, Luca Busetto, Djordje S. Popovic, and et al. 2025. "Preliminary Study on Circulating REG3α and Its Associations with Vitamin D Supplementation and Inflammatory Biomarkers in Adults with Overweight and Obesity" Current Issues in Molecular Biology 47, no. 12: 970. https://doi.org/10.3390/cimb47120970

APA Style

Koufakis, T., Kouroupis, D., Kourti, A., Karalazou, P., Thisiadou, K., Georgiadis, I., Mustafa, O., Maltese, G., Busetto, L., Popovic, D. S., Giouleme, O., Kotsa, K., Doumas, M., & Makedou, K. (2025). Preliminary Study on Circulating REG3α and Its Associations with Vitamin D Supplementation and Inflammatory Biomarkers in Adults with Overweight and Obesity. Current Issues in Molecular Biology, 47(12), 970. https://doi.org/10.3390/cimb47120970

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