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J Endocrinol. 2013 Jan 18;216(2):265-71. doi: 10.1530/JOE-12-0344. Print 2013 Feb.

1,25-Dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue.

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Laboratory of Metabolic Disease Research and Drug Development, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.


Leptin is an adipose tissue-derived hormone that plays a critical role in energy homeostasis. Vitamin D has been shown to regulate energy metabolism, but the relationship between vitamin D and leptin is unclear. Leptin expression and secretion was reduced in vitamin D receptor (VDR)-null mice and increased in transgenic (Tg) mice overexpressing the VDR in adipocytes; however, as leptin is mainly determined by fat mass, it is unclear whether the vitamin D hormone directly regulates leptin expression. To address this question, we determined the effect of vitamin D on leptin expression in vivo and ex vivo. One-week treatment of WT mice with the vitamin D analog RO-27-5646 led to a significant increase in adipose leptin mRNA transcript and serum leptin levels. Moreover, in adipose tissue cultures, 1,25-dihydroxyvitamin D markedly stimulated mRNA expression and secretion of leptin, but not resistin, in adipose tissues obtained from WT mice, but not from VDR-null mice, and leptin upregulation induced by 1,25-dihydroxyvitamin D was more robust in adipose tissues obtained from VDR Tg mice compared with WT mice. These data demonstrate that 1,25-dihydroxyvitamin D stimulates adipose leptin production in a VDR-dependent manner, suggesting that vitamin D may affect energy homeostasis through direct regulation of leptin expression.

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