1,25‑Dihydroxyvitamin D3 mitigates the adipogenesis induced by bisphenol A in 3T3-L1 and hAMSC through miR-27-3p regulation

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

International Journal of Obesity Pub Date : 2024-09-10 DOI:10.1038/s41366-024-01629-w

Donatella Paola Provvisiero, Mariarosaria Negri, Feliciana Amatrudo, Roberta Patalano, Tatiana Montò, Cristina de Angelis, Chiara Graziadio, Gabriella Pugliese, Giulia de Alteriis, Annamaria Colao, Rosario Pivonello, Silvia Savastano, Claudia Pivonello

{"title":"1,25‑Dihydroxyvitamin D3 mitigates the adipogenesis induced by bisphenol A in 3T3-L1 and hAMSC through miR-27-3p regulation","authors":"Donatella Paola Provvisiero, Mariarosaria Negri, Feliciana Amatrudo, Roberta Patalano, Tatiana Montò, Cristina de Angelis, Chiara Graziadio, Gabriella Pugliese, Giulia de Alteriis, Annamaria Colao, Rosario Pivonello, Silvia Savastano, Claudia Pivonello","doi":"10.1038/s41366-024-01629-w","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Endocrine-disrupting compounds, including bisphenol A (BPA), may promote obesity influencing basal metabolic rate and shifting metabolism towards energy storage. The role of 1,25‑Dihydroxyvitamin D3 (VitD) in counteracting adipogenesis is still a matter of debate. Thus, the current study aims to investigate whether and how VitD exposure during adipogenesis could prevent the pro-adipogenic effect of BPA in two adipocyte models, mouse 3T3-L1 cell line and human adipose-derived mesenchymal stem cells (hAMSC).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>3T3-L1, mouse pre-adipocytes and human adipose-derived mesenchymal stem cells (hAMSC) were treated with VitD (10<sup>−7</sup> M) and BPA (10<sup>−8</sup> M and 10<sup>−9</sup> M), alone or in combination, throughout the differentiation in mature adipocytes. Cellular lipid droplet accumulation was assessed by Oil Red O staining, mRNA and protein expression of key adipogenic markers, transcription factors, and cytokines were investigated by RT-qPCR and WB, respectively. miRNAs involved in the regulation of adipogenic transcription factors were evaluated by RT-qPCR, and highly potent steric-blocking oligonucleotides (miRNA inhibitors) were used to modulate miRNAs expression.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Pre-adipocytes express VitD receptor (VDR) in basal condition, but during the differentiation process VDR expression reduces if not stimulated by the ligand. VitD significantly decreases lipid accumulation, with a consequent reduction in adipogenic marker expression, and counteracts the pro-adipogenic effect of BPA in 3T3-L1 and hAMSC during differentiation. This effect is associated to the increased expression of miR-27a-3p and miR-27b-3p. The blocking of miR-27a-3p and miR-27b-3p through miRNA inhibitors prevents the anti-adipogenic effect of VitD in both cell models.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>These results suggest that in cultured 3T3-L1 and hAMSC VitD induces an anti-adipogenic effect and prevents BPA pro-adipogenic effect by triggering at least in part epigenetic mechanisms involving miR-27-3p.</p><figure></figure>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Obesity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41366-024-01629-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose

Endocrine-disrupting compounds, including bisphenol A (BPA), may promote obesity influencing basal metabolic rate and shifting metabolism towards energy storage. The role of 1,25‑Dihydroxyvitamin D3 (VitD) in counteracting adipogenesis is still a matter of debate. Thus, the current study aims to investigate whether and how VitD exposure during adipogenesis could prevent the pro-adipogenic effect of BPA in two adipocyte models, mouse 3T3-L1 cell line and human adipose-derived mesenchymal stem cells (hAMSC).

Methods

3T3-L1, mouse pre-adipocytes and human adipose-derived mesenchymal stem cells (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 adipocytes. Cellular lipid droplet accumulation was assessed by Oil Red O staining, mRNA and protein expression of key adipogenic markers, transcription factors, and cytokines were investigated by RT-qPCR and WB, respectively. miRNAs involved in the regulation of adipogenic transcription factors were evaluated by RT-qPCR, and highly potent steric-blocking oligonucleotides (miRNA inhibitors) were used to modulate miRNAs expression.

Results

Pre-adipocytes express VitD receptor (VDR) in basal condition, but during the differentiation process VDR expression reduces if not stimulated by the ligand. VitD significantly decreases lipid accumulation, with a consequent reduction in adipogenic marker expression, and counteracts the pro-adipogenic effect of BPA in 3T3-L1 and hAMSC during differentiation. This effect is associated to the increased expression of miR-27a-3p and miR-27b-3p. The blocking of miR-27a-3p and miR-27b-3p through miRNA inhibitors prevents the anti-adipogenic effect of VitD in both cell models.

Conclusions

These results suggest that in cultured 3T3-L1 and hAMSC VitD induces an anti-adipogenic effect and prevents BPA pro-adipogenic effect by triggering at least in part epigenetic mechanisms involving miR-27-3p.

Abstract Image

查看原文本刊更多论文

1,25-二羟维生素 D3 通过调控 miR-27-3p 减轻双酚 A 诱导的 3T3-L1 和 hAMSC 脂肪生成

目的包括双酚 A（BPA）在内的干扰内分泌的化合物可能会促进肥胖，影响基础代谢率并使新陈代谢转向能量储存。1,25-二羟维生素 D3（VitD）在抑制脂肪生成方面的作用仍存在争议。因此，本研究旨在探讨在两种脂肪细胞模型（小鼠 3T3-L1 细胞系和人脂肪间充质干细胞（hAMSC））中，脂肪生成过程中暴露于 VitD 是否以及如何阻止双酚 A 的促脂肪生成效应。方法在成熟脂肪细胞的整个分化过程中，单独或联合使用 VitD（10-7 M）和 BPA（10-8 M 和 10-9 M）处理 3T3-L1、小鼠前脂肪细胞和人脂肪间充质干细胞（hAMSC）。用油红 O 染色法评估细胞脂滴的积累，用 RT-qPCR 和 WB 分别检测关键脂肪生成标志物、转录因子和细胞因子的 mRNA 和蛋白表达。结果前期脂肪细胞在基础状态下会表达 VitD 受体（VDR），但在分化过程中，如果没有配体的刺激，VDR 的表达会降低。在 3T3-L1 和 hAMSC 的分化过程中，VitD 能明显降低脂质积累，从而减少脂肪生成标志物的表达，并抵消双酚 A 的促脂肪生成作用。这种效应与 miR-27a-3p 和 miR-27b-3p 的表达增加有关。结论：这些结果表明，在培养的 3T3-L1 和 hAMSC 中，VitD 通过触发至少部分涉及 miR-27-3p 的表观遗传学机制，诱导了抗致脂作用，并阻止了 BPA 的促致脂作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

International Journal of Obesity 医学-内分泌学与代谢

CiteScore

10.00

自引率

2.00%

发文量

221

审稿时长

3 months

期刊介绍： The International Journal of Obesity is a multi-disciplinary forum for research describing basic, clinical and applied studies in biochemistry, physiology, genetics and nutrition, molecular, metabolic, psychological and epidemiological aspects of obesity and related disorders. We publish a range of content types including original research articles, technical reports, reviews, correspondence and brief communications that elaborate on significant advances in the field and cover topical issues.