Cold-induced Yes-associated-protein expression through miR-429 mediates the browning of white adipose tissue
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...
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Veröffentlicht in: | Science China. Life sciences 2021-03, Vol.64 (3), p.404-418 |
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Sprache: | eng |
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Zusammenfassung: | 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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ISSN: | 1674-7305 1869-1889 |
DOI: | 10.1007/s11427-020-1779-2 |