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 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.