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":"1,25-二羟维生素 D3 通过调控 miR-27-3p 减轻双酚 A 诱导的 3T3-L1 和 hAMSC 脂肪生成","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":"{\"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}","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}
1,25‑Dihydroxyvitamin D3 mitigates the adipogenesis induced by bisphenol A in 3T3-L1 and hAMSC through miR-27-3p regulation
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.
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.
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