Contributors: Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina = Biomedical Research Institute of Málaga and Nanomedicine Platform (IBIMA Plataforma BIONAND ); Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga Spain; CIBER OBN, Biomedical Research Networking Center for Physiopathology of Obesity and Nutrition; Universidad Carlos III de Madrid Madrid (UC3M); Universidad de Málaga Málaga = University of Málaga Málaga; Universidad de Sevilla = University of Seville; Universidad de Córdoba = University of Córdoba Córdoba; Hospital Universitario Virgen Macarena Séville; Hospital Universitario Virgen de la Victoria = Virgen de la Victoria University Hospital; Instituto de Biomedicina de Sevilla; Hospital Universitario Virgen del Rocío Sevilla; Recherche translationnelle sur le diabète - U 1190 (RTD); Institut Pasteur de Lille; Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Université de Lille-Université de Lille; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM); Instituto de Salud Carlos III Madrid (ISC); This research was supported by the following grants: This study has been funded by Instituto de Salud Carlos III (ISCIII) through the projectPI21/01924 and PI18/00785 and co-funded by the European Union, by the Consejería de Transformacion Economica, Industria, Conocimiento yUniversidades-Junta de Andalucía and ERDF-EU (PI20-01274) and by University of Sevilla VI PP USO SSGG (2021/00001297). PI-0092–2017and PI-0235–2021 from Consejeria de Salud (Junta de Andalucia), Spain. S.L. is a recipient of a Plan Andaluz de Investigaci´on, Desarrollo eInnovaci´on post-doctoral grant from the Consejería de Economía, Conocimiento, Empresas y Universidades (DOC-01138). A.M.G. was arecipient of a Plan Propio de Investigaci´on, Transferencia y Divulgacion Científica postdoctoral grant from University of M´alaga. FJBS, andREBAV-R are under contract with the ‘Nicolas Monardes’ program from the Servicio Andaluz de Salud, Consejería de Salud y Consumo-Junta deAndalucía (RC-0001-2021, RC-0006-2020 and C-0060-2018, respectively. A.V-R. was supported by a grant from the Ministerio de Economíay Competitividad (Proyectos I+D+i para J´ovenes Investigadores, SAF2014-60649-JIN).
نبذة مختصرة : International audience ; Despite the abundance of registered clinical trials worldwide, the availability of effective drugs for obesity treatment is limited due to their associated side effects. Thus, there is growing interest in therapies that stimulate energy expenditure in white adipose tissue. Recently, we demonstrated that the delivery of a miR-21 mimic using JetPEI effectively inhibits weight gain in an obese mouse model by promoting metabolism, browning, and thermogenesis, suggesting the potential of miR-21 mimic as a treatment for obesity. Despite these promising results, the implementation of more advanced delivery system techniques for miR-21 mimic would greatly enhance the advancement of safe and efficient treatment approaches for individuals with obesity in the future. Our objective is to explore whether a new delivery system based on gold nanoparticles and Gemini surfactants (Au@16-ph-16) can replicate the favorable effects of the miR-21 mimic on weight gain, browning, and thermogenesis. We found that dosages as low as 0.2 μg miR-21 mimic /animal significantly inhibited weight gain and induced browning and thermogenic parameters. This was evidenced by the upregulation of specific genes and proteins associated with these processes, as well as the biogenesis of beige adipocytes and mitochondria. Significant increases in miR-21 levels were observed in adipose tissue but not in other tissue types. Our data indicates that Au@16-ph-16 could serve as an effective delivery system for miRNA mimics, suggesting its potential suitability for the development of future clinical treatments against obesity.
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