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Preliminary Study on Circulating REG3α and Its Associations with Vitamin D Supplementation and Inflammatory
Theocharis Koufakis1, Dimitrios Kouroupis1, Areti Kourti2
1Second Propaedeutic Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, Greece.
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.
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