RT Journal Article
T1 miR-21 mimic blocks obesity in mice: A novel therapeutic option.
A1 Lhamyani, Said
A1 Gentile, Adriana-Mariel
A1 Giráldez-Pérez, Rosa M
A1 Feijóo-Cuaresma, Mónica
A1 Romero-Zerbo, Silvana Yanina
A1 Clemente-Postigo, Mercedes
A1 Zayed, Hatem
A1 Olivera, Wilfredo Oliva
A1 Bermúdez-Silva, Francisco Javier
A1 Salas, Julián
A1 Gómez, Carlos López
A1 Hmadcha, Abdelkrim
A1 Hajji, Nabil
A1 Olveira, Gabriel
A1 Tinahones, Francisco J
A1 El Bekay, Rajaa
K1 TMEM26
K1 adipose tissue
K1 brown adipose tissue
K1 browning
K1 diabetes
K1 metabolism
K1 miR-21
K1 obesity
K1 thermogenesis
K1 uncoupling protein 1
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 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.
SN 2162-2531
YR 2021
FD 2021-07-02
LK https://hdl.handle.net/10668/27753
UL https://hdl.handle.net/10668/27753
LA en
DS RISalud
RD Apr 8, 2025