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Leptin blocks the inhibitory effect of vitamin D on adipogenesis and cell proliferation in 3T3-L1 adipocytes.

Abstract：

:Recently, we demonstrated high serum leptin and 25(OH)D (calcidiol) in obese animals, with high C/EBPβ and PPARγ expression in adipose tissue. Since the role of vitamin D in adipogenesis remains controversial and hyperleptinemia is found in obesity, we asked if leptin could interfere in vitamin D action on adipocytes. Here, we studied the direct effect of these two hormones upon 3T3L1 preadipocytes incubated with or without 1,25(OH)2D (100 nM, 24 h) and with leptin (10-7 M, 4 h later). RT-PCR (VDR and Cyp27b1/1α-hydroxylase), western blotting (VDR, Cyp27b1/1α-hydroxylase, ObR-b, C/EBPβ, PPARγ and Bax content), a cell proliferation assay and an Annexin V-FITC binding assay were performed. Incubation with 1,25(OH)2D decreased Cyp27b1/1α-hydroxylase and VDR. Co-incubation of 1,25(OH)2D and leptin did not change Cyp27b1/1α-hydroxylase and had no additive effect upon the decreased VDR mRNA. Incubation with 1,25(OH)2D decreased C/EBPβ and PPARγ. In the cell proliferation assay, 1,25(OH)2D decreased the number of 3T3L1 cells. No changes in OBR-b or apoptotic parameters (Bax and annexin-V) were observed. The 1,25(OH)2D decreased pro-adipogenic factors and proliferation of adipocytes. However, since it inhibits the conversion of 25(OH)D to 1,25(OH)2D and VDR mRNA long-term, it could decrease the vitamin D response in adipocytes, leading to greater adipogenesis. The co-incubation of both hormones, simulating what occurs in obesity, even neutralizing the effect on Cyp27b1/1α-hydroxylase, did not change the vitamin D sensitivity but decreased SOCS-3 and pSTAT-3. Thus, an excess of vitamin D and hyperleptinemia could decrease vitamin D sensitivity in adipocytes, contributing to increased adipogenesis.

journal_name

Gen Comp Endocrinol

journal_title

General and comparative endocrinology

authors

Nobre JL,Lisboa PC,Carvalho JC,Martins MR,Vargas S,Barja-Fidalgo C,de Moura EG,de Oliveira E

doi

10.1016/j.ygcen.2018.01.014

subject

Has Abstract

pub_date

2018-09-15 00:00:00

pages

1-8

eissn

0016-6480

issn

1095-6840

pii

S0016-6480(17)30624-X

journal_volume

266

pub_type

杂志文章

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Leptin blocks the inhibitory effect of vitamin D on adipogenesis and cell proliferation in 3T3-L1 adipocytes.