1. miR-21 blocks obesity in mice: a potential therapy for humans
- Author
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Rosa M. Giráldez-Pérez, Nabil Hajji, Francisco Javier Bermúdez-Silva, Rajaa El Bekay, Mónica Feijóo-Cuaresma, Gabriel Olveira Fuster, Said Lhamyani, Adriana-Mariel Gentile, Julián Salas, Carlos López Gómez, Wilfredo Oliva Olivera, Francisco J. Tinahones, Hatem Zayed, Silvana Y. Romero-Zerbo, and Mercedes Clemente-Postigo
- Subjects
medicine.medical_specialty ,business.industry ,White adipose tissue ,medicine.disease ,Obesity ,Insulin resistance ,Endocrinology ,Adipogenesis ,Internal medicine ,Diabetes mellitus ,microRNA ,Metabolically healthy obesity ,medicine ,business ,Thermogenesis - Abstract
microRNAs are promising drug targets in obesity and metabolic disorders. miR-21 expression is upregulated in obese white adipose tissue (WAT); however, its physiological role in WAT has not been fully explored. We aimed to dissect the underlying molecular mechanisms of miR-21 in treating obesity, diabetes, and insulin resistance. We demonstrated, in human and mice, that elevated miR-21 expression is associated with metabolically healthy obesity. miR-21 mimic affected the expression of genes associated with adipogenesis, thermogenesis, and browning in 3T3-L1 adipocytes. In addition, it blocked high fat diet-induced weight gain in obese mice, without modifying food intake or physical activity. This was associated with metabolic enhancements, WAT browning and thermogenic programming, and brown AT induction through VEGF-A, p53, and TGFβ1 signaling pathways. Our findings add a novel role of miR-21 in the regulation of obesity and a potential therapy for both obesity and T2D without altering caloric intake and physical activities.
- Published
- 2020