miR-21 mimic blocks obesity in mice: A novel therapeutic option

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 tiss...

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Main Authors: Said Lhamyani (Author), Adriana-Mariel Gentile (Author), Rosa M. Giráldez-Pérez (Author), Mónica Feijóo-Cuaresma (Author), Silvana Yanina Romero-Zerbo (Author), Mercedes Clemente-Postigo (Author), Hatem Zayed (Author), Wilfredo Oliva-Olivera (Author), Francisco Javier Bermúdez-Silva (Author), Julián Salas (Author), Carlos López Gómez (Author), Abdelkrim Hmadcha (Author), Nabil Hajji (Author), Gabriel Olveira (Author), Francisco J. Tinahones (Author), Rajaa El Bekay (Author)
Format: Book
Published: Elsevier, 2021-12-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Said Lhamyani  |e author 
700 1 0 |a Adriana-Mariel Gentile  |e author 
700 1 0 |a Rosa M. Giráldez-Pérez  |e author 
700 1 0 |a Mónica Feijóo-Cuaresma  |e author 
700 1 0 |a Silvana Yanina Romero-Zerbo  |e author 
700 1 0 |a Mercedes Clemente-Postigo  |e author 
700 1 0 |a Hatem Zayed  |e author 
700 1 0 |a Wilfredo Oliva-Olivera  |e author 
700 1 0 |a Francisco Javier Bermúdez-Silva  |e author 
700 1 0 |a Julián Salas  |e author 
700 1 0 |a Carlos López Gómez  |e author 
700 1 0 |a Abdelkrim Hmadcha  |e author 
700 1 0 |a Nabil Hajji  |e author 
700 1 0 |a Gabriel Olveira  |e author 
700 1 0 |a Francisco J. Tinahones  |e author 
700 1 0 |a Rajaa El Bekay  |e author 
245 0 0 |a miR-21 mimic blocks obesity in mice: A novel therapeutic option 
260 |b Elsevier,   |c 2021-12-01T00:00:00Z. 
500 |a 2162-2531 
500 |a 10.1016/j.omtn.2021.06.019 
520 |a 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. 
546 |a EN 
690 |a obesity 
690 |a miR-21 
690 |a adipose tissue 
690 |a thermogenesis 
690 |a browning 
690 |a brown adipose tissue 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Molecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 401-416 (2021) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2162253121001608 
787 0 |n https://doaj.org/toc/2162-2531 
856 4 1 |u https://doaj.org/article/322e93f98c5a4bea87e9981e94c70da2  |z Connect to this object online.