Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human Adipocytes.

adipogenesis automated quantitative image analysis lipid nanoparticles microRNA

Journal

Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003

Informations de publication

Date de publication:
19 Jul 2023
Historique:
received: 15 06 2023
revised: 12 07 2023
accepted: 16 07 2023
medline: 29 7 2023
pubmed: 29 7 2023
entrez: 29 7 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37514169
pii: pharmaceutics15071983
doi: 10.3390/pharmaceutics15071983
pmc: PMC10384627
pii:
doi:

Types de publication

Journal Article

Langues

eng

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Auteurs

Anna-Laurence Schachner-Nedherer (AL)

Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria.
Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria.

Julia Fuchs (J)

Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria.

Ivan Vidakovic (I)

Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria.

Oliver Höller (O)

Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria.

Gebhard Schratter (G)

Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria.

Gunter Almer (G)

Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8010 Graz, Austria.

Eleonore Fröhlich (E)

Center for Medical Research, Medical University of Graz, 8010 Graz, Austria.

Andreas Zimmer (A)

Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria.

Martin Wabitsch (M)

Division of Pediatric Endocrinology, Diabetes Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, 89075 Ulm, Germany.

Karin Kornmueller (K)

Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria.

Ruth Prassl (R)

Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria.

Classifications MeSH