RT Journal Article
T1 miR-21 mimic blocks obesity in mice: A novel therapeutic option
A1 Lhamyani, Said
A1 Gentile, Adriana-Mariel
A1 Giraldez-Perez, Rosa M.
A1 Feijoo-Cuaresma, Monica
A1 Romero-Zerbo, Silvana Yanina
A1 Clemente-Postigo, Mercedes
A1 Zayed, Hatem
A1 Olivera, Wilfredo Oliva
A1 Bermudez-Silva, Francisco Javier
A1 Salas, Julian
A1 Lopez Gomez, Carlos
A1 Hmadcha, Abdelkrim
A1 Hajji, Nabil
A1 Olveira, Gabriel
A1 Tinahones, Francisco J.
A1 El Bekay, Rajaa
K1 Adipose-tissue dysfunction
K1 Insulin-resistance
K1 Brown
K1 Fat
AB MicroRNAs (miRNAs) are promising drug targets for obesity and metabolic disorders. Recently, miRNA mimics are providing a unique mechanism of action that guides the process for drug development and sets out the context of their therapeutic application. miRNA (miR)-21 expression in white adipose tissue (WAT) has been associated with obesity. We aimed to analyze miR-21 expression levels in relation to diabetes and obesity to determine the effect that miR-21 mimic has on processes involved in WAT functionality, to dissect the underlying molecular mechanisms, and to study the potential therapeutic application of the miR-21 mimic against obesity. We found higher miR-21 levels in WAT from non-diabetic obese compared to normoweight humans and mice. Moreover, in 3T3-L1 adipocytes, miR-21 mimic affect genes involved in WAT functionality regulation and significantly increase the expression of genes involved in browning and thermogenesis. Interestingly, in vivo treatment with the miR-21 mimic blocked weight gain induced by a high-fat diet in obese mice, without modifying food intake or physical activity. This was associated with metabolic enhancement, WAT browning, and brown adipose tissue (AT) thermogenic programming through vascular endothelial growth factor A (VEGF-A), p53, and transforming growth factor beta 1 (TGF-beta 1) signaling pathways. Our findings suggest that miR-21 mimic-based therapy may provide a new opportunity to therapeutically manage obesity and consequently, its associated alterations.
PB Cell press
SN 2162-2531
YR 2021
FD 2021-06-25
LK http://hdl.handle.net/10668/18860
UL http://hdl.handle.net/10668/18860
LA en
NO Lhamyani S, Gentile AM, Giráldez-Pérez RM, Feijóo-Cuaresma M, Romero-Zerbo SY, Clemente-Postigo M, et al. miR-21 mimic blocks obesity in mice: A novel therapeutic option. Mol Ther Nucleic Acids. 2021 Jul 2;26:401-416
NO The authors wish to thank all of the subjects for their collaboration. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn) is part of the “Instituto de Salud del Carlos III” (ISCIII) project. This work was supported, in part, by grants from ISCIII and co-funded by Fondo Europeo de Desarrollo Regional (FEDER)-Unión Europea (UE) (PI18/00785) and Consejería de Salud, Junta de Andalucía (PI0092-2017), Spain, and co-funded by FEDER. R.E.B. and F.J.B.-S. areunder a contract from the “Nicolas Monarde” (C-0030-2016, RC0005-2016) program from the Servicio Andaluz de Salud, Regional Ministry of Health of the Andalusian Government, Andalusia, Spain. S.L. was a recipient of postdoctoral grant Plan Andaluz de Investigación Desarrollo e Innovación (DOC-01138) from Consejería de Economía, Empresas y Universidades. A.-M.G. was a recipient of a postdoctoral grant Plan Propio de Investigación, Transferencia y Divulgación Científica, from Málaga University. M.C.-P. was recipient of a postdoctoral grant Juan de la Cierva Formación (FJCI2017-32194) from the Ministerio de Ciencia, Innovación y Universidades (Spain), and postdoctoral research grant Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020) (DOC_00448)from the Consejeria de Economía, Industria, Conocimiento y Universidades (Junta de Andalucía), Spain, co-funded by FEDER.
DS RISalud
RD Apr 8, 2025