Nickan Research Institute Journal of Parathyroid Disease 2345-6558 14 1 2026 01 01 Beyond deficiency; bidirectional metabolic dysregulation between adipose tissue inflammation and vitamin D bioavailability in pediatric obesity e13315 e13315 10.34172/jpd.2026.13315 EN Abbas Boskabadi https://orcid.org/0000-0002-0079-5312 Sara Amini https://orcid.org/0000-0002-2926-9885 Baharak Maddahi https://orcid.org/0000-0002-6067-8011 Fariba Jafari Khabaz https://orcid.org/0000-0002-1956-5795 Mahsa Asadollahi Hamedani https://orcid.org/0000-0002-7130-1201 Seyed Hossein Saadat https://orcid.org/0000-0002-6228-4438 Journal Article 10.34172/jpd.2026.13315 2025 12 01 2026 03 28 Pediatric obesity is characterized by a bidirectional metabolic dysregulation of vitamin D metabolism within adipose tissue, creating a state of functional deficiency that standard serum measurements often underestimate. Expanded adipose mass acts as a volumetric sink, sequestering fat-soluble vitamin D metabolites and contributing to low circulating 25-hydroxyvitamin D levels, inversely correlated with body fat. Crucially, adipose tissue inflammation drives profound local metabolic disruption, where pro-inflammatory cytokines (TNF-α, IL-6) down-regulate the activating enzyme CYP27B1 (1α-hydroxylase) and upregulate the degrading enzyme CYP24A1 (24-hydroxylase) in adipocytes and macrophages. This ‘double hit’ severely diminishes 1,25-dihydroxyvitamin D [1,25(OH)2D] within the adipose microenvironment, impairing vitamin D receptor (VDR) signaling precisely where it is needed to suppress inflammation. Systemic inflammation further compromises vitamin D status by reducing hepatic CYP2R1 activity, limiting the conversion of vitamin D to 25(OH) D. Additionally, obesity-associated alterations in vitamin D-binding protein (DBP) levels and isoforms may reduce the bioavailable (free) fraction of vitamin D metabolites, exacerbating tissue-level deficiency despite potentially borderline total serum 25(OH)D. Consequently, the combination of sequestration, inflammation-induced dysregulation of activating/degrading enzymes, and altered binding protein dynamics creates a significant disconnect, where standard serum 25(OH)D levels fail to reflect the critical local deficiency of bioactive vitamin D within the inflamed adipose tissue of obese children. This tissue-specific functional deficiency, driven by inflammation, underpins the impaired immunomodulation and perpetuates metabolic dysfunction, highlighting the inadequacy of conventional vitamin D assessment in obesity and necessitating consideration of bioavailability and tissue metabolism.