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AuthorLhamyani, Said
AuthorGentile, Adriana-Mariel
AuthorGiráldez-Pérez, Rosa M
AuthorFeijóo-Cuaresma, Mónica
AuthorRomero-Zerbo, Silvana Yanina
AuthorClemente-Postigo, Mercedes
AuthorZayed, Hatem
AuthorOlivera, Wilfredo Oliva
AuthorBermúdez-Silva, Francisco Javier
AuthorSalas, Julián
AuthorGómez, Carlos López
AuthorHmadcha, Abdelkrim
AuthorHajji, Nabil
AuthorOlveira, Gabriel
AuthorTinahones, Francisco J
AuthorEl Bekay, Rajaa
Available date2021-11-29T09:35:25Z
Publication Date2021-12-03
Publication NameMolecular Therapy Nucleic Acids
Identifierhttp://dx.doi.org/10.1016/j.omtn.2021.06.019
CitationSaid Lhamyani et. al. miR-21 mimic blocks obesity in mice: A novel therapeutic option, Molecular Therapy - Nucleic Acids, Volume 26, 2021, Pages 401-416, ISSN 2162-2531, https://doi.org/10.1016/j.omtn.2021.06.019.
ISSN2162-2531
URIhttp://hdl.handle.net/10576/25184
AbstractMicroRNAs (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, 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.
Languageen
PublisherElsevier
SubjectTMEM26
adipose tissue
brown adipose tissue
browning
diabetes
metabolism
miR-21
obesity
thermogenesis
uncoupling protein 1
TitlemiR-21 mimic blocks obesity in mice: A novel therapeutic option
TypeArticle
Pagination401-416
Volume Number26
dc.accessType Open Access


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