Fig. 3: The potential modulatory role of vitamin D deficiency in obesity-related metabolomic remodeling.

Obesity is the primary driver, inducing coordinated alterations across four key metabolic pathways: lipoprotein remodeling, fatty acid shifts, amino acid imbalance, and systemic inflammation. These pathways converge on an adverse outcome defined by an atherogenic and insulin-resistant metabolic profile. Vitamin D deficiency acts as a context-dependent modifier, influencing each pathway through distinct mechanisms: (i) impaired regulation of hepatic lipid metabolism and lipoprotein enzymes (LPL, CETP), aggravating VLDL enrichment and HDL dysfunction; (ii) reduced control of lipid synthesis and fatty acid oxidation, promoting metabolic inflexibility; (iii) diminished effects on insulin sensitivity and mitochondrial function, amplifying BCAA accumulation and Gly depletion; and (iv) loss of anti-inflammatory signaling, contributing to systemic inflammation. Together, these interactions suggest that vitamin D deficiency may amplify obesity-related metabolic risk.