Uçar Nazlı, Pickering Richard T, Mueller Peter M, Deeney Jude T, Morales Suárez-Varela María, Soriano José Miguel, Holick Michael F
Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Research Group in Social and Nutritional Epidemiology, Pharmacoepidemiology and Public Health, Department of Preventive Medicine and Public Health, Food Sciences, Toxicology and Legal Medicine, School of Pharmacy and Food Sciences, Universitat de Valencia, Avenida Vicent Andres Estelles s/n, 46100 Burjassot, Valencia, Spain.
Nutrients. 2025 Jun 25;17(13):2107. doi: 10.3390/nu17132107.
Vitamin D is predominantly sequestered in adipose tissue, where it is slowly mobilized under conditions of deficiency in vivo. However, the kinetics of its uptake, release, and interaction with its major metabolites, 25(OH)D and 1,25(OH)D, remain poorly understood. Given the close relationship between obesity, low-grade chronic inflammation, and disrupted vitamin D metabolism, a clearer understanding of these dynamics in adipocytes is essential. Thus, we sought to characterize time-dependent uptake and metabolites in differentiated human adipocytes. Human pre-adipocytes were differentiated in vitro and exposed to either vitamin D and 1,25(OH)D or the combination of vitamin D, 25(OH)D and 1,25(OH)D. Intracellular concentrations were quantified through HPLC at various time points. A separate efflux experiment assessed vitamin D release under basal and isoproterenol-stimulated conditions using H-vitamin D and scintillation counting. Vitamin D uptake showed a gradual and sustained increase over 96 h, suggesting ongoing accumulation within lipid-rich compartments. In contrast, 25(OH)D and 1,25(OH)D peaked rapidly within the first hour and declined sharply. Isoproterenol stimulation significantly enhanced vitamin D release into the extracellular medium from the adipocytes, indicating increased efflux during lipolytic activation. Adipocytes selectively retain vitamin D while rapidly clearing its hydroxylated forms. These findings highlight the distinct intracellular handling of vitamin D metabolites and suggest that tailored supplementation strategies-particularly in individuals with excess adiposity-may improve bioavailability and metabolic efficacy.
维生素D主要储存在脂肪组织中，在体内缺乏的情况下会缓慢释放。然而，其摄取、释放以及与主要代谢产物25(OH)D和1,25(OH)D相互作用的动力学仍知之甚少。鉴于肥胖、低度慢性炎症与维生素D代谢紊乱之间的密切关系，更清楚地了解脂肪细胞中的这些动态变化至关重要。因此，我们试图描述分化的人脂肪细胞中维生素D随时间的摄取情况及其代谢产物。人前脂肪细胞在体外分化，并分别暴露于维生素D和1,25(OH)D，或维生素D、25(OH)D和1,25(OH)D的组合。通过高效液相色谱法在不同时间点对细胞内浓度进行定量。另一个流出实验使用H-维生素D和闪烁计数法评估了在基础条件和异丙肾上腺素刺激条件下维生素D的释放。维生素D的摄取在96小时内呈逐渐持续增加，表明在富含脂质的区室中不断积累。相比之下，25(OH)D和1,25(OH)D在第一小时内迅速达到峰值，然后急剧下降。异丙肾上腺素刺激显著增强了脂肪细胞向细胞外培养基中释放维生素D，表明在脂解激活过程中流出增加。脂肪细胞选择性地保留维生素D，同时迅速清除其羟基化形式。这些发现突出了维生素D代谢产物在细胞内的不同处理方式，并表明定制的补充策略——尤其是对于肥胖个体——可能会提高生物利用度和代谢效果。
