3 years ago

Glucocorticoids suppressing the browning of adipose tissue via miR-19b in male mice.

Guoxian Ding, Jing Yu, Xiaocen Kong, Yunlu Sheng, Wenjuan Di, Juan Liu, Yifan Lv, Min Huang, Hui Liang, Hong Zhou
Physiological levels of glucocorticoids are required for proper metabolic control, and excessive glucocorticoid action has been linked to a variety of pandemic metabolic diseases. microRNA (miRNA)-19b plays a critical role in the pathogenesis of glucocorticoid-induced metabolic diseases. This study sought to explore the potential of miRNA-based therapeutics targeting adipose tissue. Our results showed that overexpressed miR-19b in stromal vascular fraction cells derived from subcutaneous adipose tissue had the same effects as dexamethasone treatment on the inhibition of adipose browning and oxygen consumption rate. The inhibition of miR-19b blocked dexamethasone -mediated suppression of the expression of browning marker genes as well as the oxygen consumption rate in differentiated stromal vascular fraction cells derived from subcutaneous and brown adipose tissue. While overexpressed miR-19b in stromal vascular fraction cells derived from brown adipose tissue also had the same effects as dexamethasone treatment on the inhibition of brown adipose differentiation and energy expenditure. Glucocorticoids transcriptionally regulate the expression of miR-19b via a glucocorticoid receptor-mediated direct DNA binding mechanism. This study confirmed that miR-19b is an essential target for glucocorticoid-mediated control of adipose tissue browning. It is hoped that the plasticity of the adipose organ can be exploited in the next generation of therapeutic strategies to combat the increasing incidence of metabolic diseases, including obesity and diabetes.

Publisher URL: http://doi.org/10.1210/en.2017-00566

DOI: 10.1210/en.2017-00566

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