ECE2024 Oral Communications Oral Communications 6: Environmental Endocrinology (6 abstracts)
1,25-Dihydroxyvitamin D3 reduces adipogenesis and mitigates the bisphenol-A-induced pro-adipogenic effect in mouse 3T3-L1 cell line and human adipose-derived mesenchymal stem cells through miR-27-3p regulation
Donatella Provvisiero 1 , Mariarosaria Negri 2 , Feliciana Amatrudo 2 , Roberta Patalano 1 , Tatiana Montò 1 , Gabriella Pugliese 1 , Giulia de Alteriis 1 , Chiara Graziadio 1 , Annamaria Colao 1 , Rosario Pivonello 1 , Silvia Savastano 1 & Claudia Pivonello 3
1Federico II University of Naples, Department of Clinical Medicine and Surgery, Naples, Italy; 2Università Telematica Pegaso, Dipartimento di Scienze Umanistiche, Naples, Italy; 3Federico II University of Naples, Department of Public Health, Naples, Italy
Endocrine-disrupting chemicals, including bisphenol A (BPA) may promote obesity. The role of 1,25-Dihydroxyvitamin D3 (VitD) in counteracting adipogenesis is still a matter of question. Thus, the current study aims to investigate whether and how VitD exposure during adipogenesis could prevent the BPA pro-adipogenic effect in adipocyte models: the mouse pre-adipocytes 3T3-L1 and the human adipose-derived mesenchymal stem cells (hAMSC). 3T3-L1 and hAMSC were treated with VitD (10-7 M) and BPA (10-8 M and 10-9 M), alone or in combination, throughout the differentiation in mature white adipocytes. Lipid droplet accumulation was assessed by RedOilO staining, mRNA and protein expression of key adipogenic markers were investigated by RT-qPCR and WB, respectively. miRNAs involved in the regulation of adipogenic transcription factors were evaluated by RT-qPCR and miRNA inhibitors were used to modulate miRNAs expression. RedOilO staining quantification evidenced a significant VitD anti-adipogenic outcome (~54%, P=0.0022) and a significant BPA pro-adipogenic outcome (~29%, P=0.047 BPA10-8 M and ~42%, P=0.047 BPA10-9 M) compared to 3T3-L1 control cells, and a significant VitD anti-adipogenic outcome (~27%, P<0.0001) and a significant BPA pro-adipogenic outcome (~8%, P=0.0007 BPA10-9 M) compared to hAMSC control cells. In both cell models VitD counterbalanced BPA pro-adipogenic effect by reducing lipid accumulation, with a maximum effect of ~76%, P=0.0022 (BPA10-9 M vs VitD+BPA10-9 M) and 34.9%, P=0.0022 (control vs VitD+BPA10-9 M)) compared with untreated 3T3-L1 cells and ~12%, P=0.0003 (BPA10-9 M vs VitD+BPA10-9 M) in hAMSC. In both 3T3-L1 and hAMSC, BPA significantly induced while VitD significantly inhibited mRNA and protein expression of the main adipogenic markers such as PPARγ, C/EBPα, leptin, adiponectin, and LPL. MiR-27a-3p and miR-27b-3p are known regulators of PPARγ. RedOilO staining revealed that miR-27a-3p and miR-27b-3p blocking prevents the anti-adipogenic effect of VitD in both cell models: in 3T3-L1 VitD significantly reduced lipid accumulation compared to untreated cells (58.5%, P=0.0002) whereas miR-27a-3p and miR-27b-3p inhibitors reverted the VitD anti-adipogenic effect (+35.8%, P=0.013 and +87.0%, P<0.0001 compared to VitD, respectively) and in hAMSC VitD significantly reduced lipid accumulation compared to untreated cells (32.9%, P<0.0001) whereas miR-27a-3p and miR-27b-3p inhibitors reverted the VitD anti-adipogenic effect (30.1%, P<0.0001 and 30.4%, P<0.0001 compared to VitD, respectively). In 3T3-L1 and hAMSC, VitD treatment reduced PPARγ, C/EBPα, adiponectin and leptin protein expression. This effect was reverted when miR-27a-3p and miR-27b-3p were blocked by inhibitors. These results suggest that VitD induces an anti-adipogenic effect and prevents BPA pro-adipogenic effect through the activation of miR-27a-3p and miR-27b-3p effectors in mature white adipocytes derived from 3T3-L1 and hAMSC.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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