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  • Title: Cold-induced Yes-associated-protein expression through miR-429 mediates the browning of white adipose tissue.
    Author: Ye C, Duan J, Zhang X, Yao L, Song Y, Wang G, Li Q, Wang B, Ai D, Wang C, Zhu Y.
    Journal: Sci China Life Sci; 2021 Mar; 64(3):404-418. PubMed ID: 32804340.
    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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