Nimitphong Hataikarn, Guo Weimin, Holick Michael F, Fried Susan K, Lee Mi-Jeong
Department of Medicine, Section of Endocrinology and Metabolism, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts, USA.
Obesity (Silver Spring). 2021 Mar;29(3):562-568. doi: 10.1002/oby.23109.
The purpose of this study was to investigate the effects of vitamin D on adipokine expression and inflammation in human adipose tissues and adipocytes and evaluate the molecular mechanisms involved.
Omental and abdominal subcutaneous human adipose tissues were treated with 1,25-dihydroxyvitamin D (1,25(OH) D ), and adipokine levels were measured. Vitamin D effects were measured with or without dexamethasone because glucocorticoids are known to affect vitamin D actions. Using RNA interference, we examined whether the vitamin D receptor (VDR) mediated vitamin D actions on adipokine expression and inflammatory signaling pathways in human adipocytes.
mRNA levels and secretion of leptin and IL-6 were suppressed by 1,25(OH) D in omental adipose tissues. Cotreatment with dexamethasone did not affect these inhibitory actions but partially blocked CYP24A1 induction. Similar results were observed in the subcutaneous depot. In addition, 1,25(OH) D suppressed leptin and IL-6 expression as well as nuclear factor-κB and extracellular signal-regulated kinase-1/2 phosphorylation in human adipocytes. Adipokine expression also was decreased by 25-hydroxyvitamin D (25(OH)D ), but not vitamin D . Knockdown of VDR increased the inflammatory signaling activity in the control condition and blocked the inhibitory effects of 1,25(OH) D on adipokine and inflammatory signaling pathways.
Vitamin D acts through VDR to inhibit inflammatory pathways and adipokine expression in human adipocytes. Increasing vitamin D status may ameliorate obesity-associated metabolic complications by decreasing adipose tissue inflammation.
本研究旨在探讨维生素D对人脂肪组织和脂肪细胞中脂肪因子表达及炎症的影响，并评估其中涉及的分子机制。
用1,25 - 二羟维生素D（1,25(OH)₂D₃）处理网膜和腹部皮下人脂肪组织，并检测脂肪因子水平。由于已知糖皮质激素会影响维生素D的作用，因此在有或没有地塞米松的情况下测量维生素D的作用。使用RNA干扰，我们研究了维生素D受体（VDR）是否介导维生素D对人脂肪细胞中脂肪因子表达和炎症信号通路的作用。
1,25(OH)₂D₃抑制网膜脂肪组织中瘦素和IL - 6的mRNA水平及分泌。与地塞米松共同处理不影响这些抑制作用，但部分阻断CYP24A1的诱导。在皮下脂肪库中观察到类似结果。此外，1,25(OH)₂D₃抑制人脂肪细胞中瘦素和IL - 6的表达以及核因子 - κB和细胞外信号调节激酶 - 1/2的磷酸化。25 - 羟维生素D（25(OH)D）也降低了脂肪因子的表达，但维生素D没有。敲低VDR在对照条件下增加了炎症信号活性，并阻断了1,25(OH)₂D₃对脂肪因子和炎症信号通路的抑制作用。
维生素D通过VDR发挥作用，抑制人脂肪细胞中的炎症通路和脂肪因子表达。提高维生素D水平可能通过减少脂肪组织炎症来改善肥胖相关的代谢并发症。
