Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human Adipocytes
Obesity and type 2 diabetes are major health burdens for which no effective therapy is available today. One treatment strategy could be to balance the metabolic functions of adipose tissue by regulating gene expressions using miRNAs. Here, we have loaded two anti-adipogenic miRNAs (miR26a and miR27a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/7/1983 |
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| author | Anna-Laurence Schachner-Nedherer Julia Fuchs Ivan Vidakovic Oliver Höller Gebhard Schratter Gunter Almer Eleonore Fröhlich Andreas Zimmer Martin Wabitsch Karin Kornmueller Ruth Prassl |
| author_facet | Anna-Laurence Schachner-Nedherer Julia Fuchs Ivan Vidakovic Oliver Höller Gebhard Schratter Gunter Almer Eleonore Fröhlich Andreas Zimmer Martin Wabitsch Karin Kornmueller Ruth Prassl |
| author_sort | Anna-Laurence Schachner-Nedherer |
| collection | DOAJ |
| description | Obesity and type 2 diabetes are major health burdens for which no effective therapy is available today. One treatment strategy could be to balance the metabolic functions of adipose tissue by regulating gene expressions using miRNAs. Here, we have loaded two anti-adipogenic miRNAs (miR26a and miR27a) into a pegylated lipid nanoparticle (PEG-LNP) formulation by a single-step microfluidic-assisted synthesis step. For the miRNA-loaded LNPs, the following system properties were determined: particle size, zeta potential, miRNA complexation efficiency, and cytotoxicity. We have used a human preadipocyte cell line to address the transfection efficiency and biological effects of the miRNA candidates at the gene and protein level. Our findings revealed that the upregulation of miR27a in preadipocytes inhibits adipogenesis by the downregulation of PPARγ and the reduction of lipid droplet formation. In contrast, miR26a transfection in adipocytes induced white adipocyte browning detected as the upregulation of uncoupling protein 1 (UCP1) as a marker of non-shivering thermogenesis. We conclude that the selective delivery of miRNAs by PEG-LNPs to adipocytes could offer new perspectives for the treatment of obesity and related metabolic diseases. |
| first_indexed | 2024-03-11T00:44:19Z |
| format | Article |
| id | doaj.art-dd27e56de2674be687157b7dcef3c6b0 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T00:44:19Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-dd27e56de2674be687157b7dcef3c6b02023-11-18T20:56:33ZengMDPI AGPharmaceutics1999-49232023-07-01157198310.3390/pharmaceutics15071983Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human AdipocytesAnna-Laurence Schachner-Nedherer0Julia Fuchs1Ivan Vidakovic2Oliver Höller3Gebhard Schratter4Gunter Almer5Eleonore Fröhlich6Andreas Zimmer7Martin Wabitsch8Karin Kornmueller9Ruth Prassl10Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, AustriaGottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, AustriaGottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, AustriaGottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, AustriaGottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, AustriaClinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8010 Graz, AustriaCenter for Medical Research, Medical University of Graz, 8010 Graz, AustriaDepartment of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, AustriaDivision of Pediatric Endocrinology, Diabetes Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, 89075 Ulm, GermanyGottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, AustriaGottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, AustriaObesity and type 2 diabetes are major health burdens for which no effective therapy is available today. One treatment strategy could be to balance the metabolic functions of adipose tissue by regulating gene expressions using miRNAs. Here, we have loaded two anti-adipogenic miRNAs (miR26a and miR27a) into a pegylated lipid nanoparticle (PEG-LNP) formulation by a single-step microfluidic-assisted synthesis step. For the miRNA-loaded LNPs, the following system properties were determined: particle size, zeta potential, miRNA complexation efficiency, and cytotoxicity. We have used a human preadipocyte cell line to address the transfection efficiency and biological effects of the miRNA candidates at the gene and protein level. Our findings revealed that the upregulation of miR27a in preadipocytes inhibits adipogenesis by the downregulation of PPARγ and the reduction of lipid droplet formation. In contrast, miR26a transfection in adipocytes induced white adipocyte browning detected as the upregulation of uncoupling protein 1 (UCP1) as a marker of non-shivering thermogenesis. We conclude that the selective delivery of miRNAs by PEG-LNPs to adipocytes could offer new perspectives for the treatment of obesity and related metabolic diseases.https://www.mdpi.com/1999-4923/15/7/1983microRNAlipid nanoparticlesadipogenesisautomated quantitative image analysis |
| spellingShingle | Anna-Laurence Schachner-Nedherer Julia Fuchs Ivan Vidakovic Oliver Höller Gebhard Schratter Gunter Almer Eleonore Fröhlich Andreas Zimmer Martin Wabitsch Karin Kornmueller Ruth Prassl Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human Adipocytes Pharmaceutics microRNA lipid nanoparticles adipogenesis automated quantitative image analysis |
| title | Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human Adipocytes |
| title_full | Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human Adipocytes |
| title_fullStr | Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human Adipocytes |
| title_full_unstemmed | Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human Adipocytes |
| title_short | Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human Adipocytes |
| title_sort | lipid nanoparticles as a shuttle for anti adipogenic mirnas to human adipocytes |
| topic | microRNA lipid nanoparticles adipogenesis automated quantitative image analysis |
| url | https://www.mdpi.com/1999-4923/15/7/1983 |
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