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Vitamin D Inhibits Adipokine Production and Inflammatory Signaling Through the Vitamin D Receptor in Human Adipocytes
Author(s) -
Nimitphong Hataikarn,
Guo Weimin,
Holick Michael F.,
Fried Susan K.,
Lee MiJeong
Publication year - 2021
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.23109
Subject(s) - adipokine , endocrinology , medicine , calcitriol receptor , adipose tissue , leptin , vitamin d and neurology , inflammation , chemistry , obesity
Objective 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. Methods Omental and abdominal subcutaneous human adipose tissues were treated with 1,25‐dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), 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. Results mRNA levels and secretion of leptin and IL‐6 were suppressed by 1,25(OH) 2 D 3 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) 2 D 3 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 3 (25(OH)D 3 ), but not vitamin D 3 . Knockdown of VDR increased the inflammatory signaling activity in the control condition and blocked the inhibitory effects of 1,25(OH) 2 D 3 on adipokine and inflammatory signaling pathways. Conclusion 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.