1. miR-21 mimic blocks obesity in mice: A novel therapeutic option
- Author
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Carlos López Gómez, Said Lhamyani, Mercedes Clemente-Postigo, Adriana-Mariel Gentile, Rosa M. Giráldez-Pérez, Nabil Hajji, Rajaa El Bekay, Abdelkrim Hmadcha, Julián Salas, Silvana Y. Romero-Zerbo, Francisco Javier Bermúdez-Silva, Gabriel Olveira, Wilfredo Oliva Olivera, Hatem Zayed, Francisco J. Tinahones, Mónica Feijóo-Cuaresma, [Lhamyani, Said] Univ Malaga, Hosp Reg Univ, Inst Invest Biomed Malaga IBIMA, Unidad Gest Clin Endocrinol & Nutr, Campus Teatinos, Malaga 29010, Spain, [Gentile, Adriana-Mariel] Univ Malaga, Hosp Reg Univ, Inst Invest Biomed Malaga IBIMA, Unidad Gest Clin Endocrinol & Nutr, Campus Teatinos, Malaga 29010, Spain, [Romero-Zerbo, Silvana Yanina] Univ Malaga, Hosp Reg Univ, Inst Invest Biomed Malaga IBIMA, Unidad Gest Clin Endocrinol & Nutr, Campus Teatinos, Malaga 29010, Spain, [Bermudez-Silva, Francisco Javier] Univ Malaga, Hosp Reg Univ, Inst Invest Biomed Malaga IBIMA, Unidad Gest Clin Endocrinol & Nutr, Campus Teatinos, Malaga 29010, Spain, [Olveira, Gabriel] Univ Malaga, Hosp Reg Univ, Inst Invest Biomed Malaga IBIMA, Unidad Gest Clin Endocrinol & Nutr, Campus Teatinos, Malaga 29010, Spain, [El Bekay, Rajaa] Univ Malaga, Hosp Reg Univ, Inst Invest Biomed Malaga IBIMA, Unidad Gest Clin Endocrinol & Nutr, Campus Teatinos, Malaga 29010, Spain, [Giraldez-Perez, Rosa M.] Univ Cordoba, Dept Biol Celular Fisiol & Inmunol, Cordoba 14004, Spain, [Feijoo-Cuaresma, Monica] Univ Malaga, Unidad Imagen Mol UIM, Ctr Invest Med Sanitarias CIMES, Malaga 2010, Spain, [Romero-Zerbo, Silvana Yanina] Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain, [Bermudez-Silva, Francisco Javier] Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain, [Hmadcha, Abdelkrim] Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain, [Olveira, Gabriel] Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain, [Clemente-Postigo, Mercedes] Univ Cordoba, Dept Cell Biol Physiol & Immunol, Maimonides Biomed Res Inst Cordoba IMIBIC, Reina Sofia Univ Hosp, Cordoba 14004, Spain, [Zayed, Hatem] Qatar Univ, Coll Hlth Sci, Dept Biomed Sci, QU Hlth, Doha 2713, Qatar, [Olivera, Wilfredo Oliva] Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, CIBER Fisiopatol Obesidad & Nutr CIBERobn, Unidad Gest Clin Endocrinol & Nutr, Madrid, Spain, [Tinahones, Francisco J.] Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, CIBER Fisiopatol Obesidad & Nutr CIBERobn, Unidad Gest Clin Endocrinol & Nutr, Madrid, Spain, [Salas, Julian] Carlos Haya Univ Hosp, Cardiovasc Surg Dept, Malaga 29009, Spain, [Lopez Gomez, Carlos] Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Unidad Gest Clin Aparato Digest, Malaga 29010, Spain, [Hmadcha, Abdelkrim] Univ Pablo de Olavide, Fundat FAID, Seville, Spain, [Hajji, Nabil] Imperial Coll London, Fac Med, Dept Surg & Canc, London W12 0HS, England, [El Bekay, Rajaa] Spanish Biomed Res Ctr Physiopathol Obes & Nutr C, Madrid, Spain, ISCIII, Fondo Europeo de Desarrollo Regional (FEDER) -Union Europea (UE), Consejeria de Salud, Junta de Andalucia, Spain, FEDER, Servicio Andaluz de Salud, Regional Ministry of Health of the Andalusian Government, Andalusia, Spain, Consejeria de Econ-omia, Empresas y Universidades, Malaga University, Ministerio de Ciencia, Innovacion y Universi-dades (Spain), and Consejeria de Economia, Industria, Conocimiento y Univer-sidades (Junta de Andalucia), Spain
- Subjects
obesity ,Adipose-tissue dysfunction ,uncoupling protein 1 ,Adipose tissue ,White ,Expression ,Context (language use) ,White adipose tissue ,RM1-950 ,Biology ,Gene ,Drug Discovery ,microRNA ,Brown adipose tissue ,medicine ,Inhibition ,browning ,Adipocyte ,diabetes ,TMEM26 ,Brown ,brown adipose tissue ,thermogenesis ,Insulin-resistance ,Thermogenin ,adipose tissue ,Vascular endothelial growth factor A ,medicine.anatomical_structure ,Fat ,Differentiation ,Cancer research ,Molecular Medicine ,Original Article ,Therapeutics. Pharmacology ,miR-21 ,Thermogenesis ,metabolism - Abstract
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 β1 (TGF-β1) 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., Graphical abstract, miR-21 mimic could serve as a potential therapeutic tool to control obesity by delaying energy storage and promoting energy expenditure in adipose tissue.
- Published
- 2021