Tissue-Specific VDR Pathway Gene Expression Is Not Associated with Circulating 25OHD in Adolescents with Severe Obesity.

Background/Objectives: Vitamin D deficiency is highly prevalent among children with obesity, but the mechanisms underlying the effectiveness of vitamin D supplementation remain poorly understood. This study examined the expression patterns of VDR-target genes across metabolically diverse tissues and compared these molecular measures with circulating serum 25-hydroxyvitamin D (25OHD), the current clinical marker of vitamin D status. We hypothesized that VDR-pathway gene expression would correlate within metabolically relevant tissues but would not be significantly associated with circulating serum 25OHD levels. Methods: A secondary analysis was performed on blood, intestinal, and visceral and subcutaneous adipose tissue (VAT and SAT, respectively) samples obtained from adolescents with obesity. Subject data included age, gender, race/ethnicity, and BMI. The tissues were analyzed via real-time qPCR to obtain quantitative levels of VDR-target gene expression, which included TLR4, THBD, and VDR in SAT and VAT and TRPV6, S100G, and VDR in intestinal tissue. Blood samples were analyzed for serum 25OHD. Results: Gene expression of THBD, VDR, and TLR4 in SAT and VAT significantly correlated with each other. In intestinal tissue, there was significant correlation between TRPV6, S100G, and VDR. No statistically significant associations were identified between the gene expression levels and serum 25OHD levels. Conclusions: VDR-target gene expression levels correlated with each other across diverse tissues but not with serum 25OHD levels. This discrepancy suggests that circulating 25OHD concentrations may not fully reflect vitamin D action.