Abstract
Targeting the white-to-brown fat conversion is important for developing potential strategies to counteract metabolic diseases; yet the mechanisms are not fully understood. Yes-associated-protein (YAP), a transcription co-activator, was demonstrated to regulate adipose tissue functions; however, its effects on browning of subcutaneous white adipose tissue (sWAT) are unclear. We demonstrated that YAP was highly expressed in cold-induced beige fat. Mechanistically, YAP was found as a target gene of miR-429, which downregulated YAP expression in vivo and in vitro. In addition, miR-429 level was decreased in cold-induced beige fat. Additionally, pharmacological inhibition of the interaction between YAP and transcriptional enhanced associate domains by verteporfin dampened the browning of sWAT. Although adipose tissue-specific YAP overexpression increased energy expenditure with increased basal uncoupling protein 1 expression, it had no additional effects on the browning of sWAT in young mice. However, we found age-related impairment of sWAT browning along with decreased YAP expression. Under these circumstances, YAP overexpression significantly improved the impaired WAT browning in middle-aged mice. In conclusion, YAP as a regulator of sWAT browning, was upregulated by lowering miR-429 level in cold-induced beige fat. Targeting the miR-429-YAP pathway could be exploited for therapeutic strategies for age-related impairment of sWAT browning.
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Acknowledgements
This work was supported by the National Key Research and Development Program of China (2019YFA0802502), the National Natural Science Foundation of China (81770836, 81822006, 81700506) and the Natural Science Foundation of Tianjin (19JCQNJC10100).
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The author(s) declare that they have no conflict of interest. The animal study conformed with the principles outlined in the Helsinki Declaration of 1975 (as revised in 2008).
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Ye, C., Duan, J., Zhang, X. et al. Cold-induced Yes-associated-protein expression through miR-429 mediates the browning of white adipose tissue. Sci. China Life Sci. 64, 404–418 (2021). https://doi.org/10.1007/s11427-020-1779-2
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DOI: https://doi.org/10.1007/s11427-020-1779-2