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miR-133a Regulates Adipocyte Browning in Vivo
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نویسنده
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liu w. ,bi p. ,shan t. ,yang x. ,yin h. ,wang y.-x. ,liu n. ,rudnicki m.a. ,kuang s.
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منبع
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plos genetics - 2013 - دوره : 9 - شماره : 7
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چکیده
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Prdm16 determines the bidirectional fate switch of skeletal muscle/brown adipose tissue (bat) and regulates the thermogenic gene program of subcutaneous white adipose tissue (sat) in mice. here we show that mir-133a,a microrna that is expressed in both bat and sats,directly targets the 3′ utr of prdm16. the expression of mir-133a dramatically decreases along the commitment and differentiation of brown preadipocytes,accompanied by the upregulation of prdm16. overexpression of mir-133a in bat and sat cells significantly inhibits,and conversely inhibition of mir-133a upregulates,prdm16 and brown adipogenesis. more importantly,double knockout of mir-133a1 and mir-133a2 in mice leads to elevations of the brown and thermogenic gene programs in sat. even 75% deletion of mir-133a (a1-/-a2+/-) genes results in browning of sat,manifested by the appearance of numerous multilocular ucp1-expressing adipocytes within sat. additionally,compared to wildtype mice,mir-133a1-/-a2+/- mice exhibit increased insulin sensitivity and glucose tolerance,and activate the thermogenic gene program more robustly upon cold exposure. these results together elucidate a crucial role of mir-133a in the regulation of adipocyte browning in vivo. © 2013 liu et al.
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آدرس
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department of animal sciences,purdue university,west lafayette,in, United States, department of animal sciences,purdue university,west lafayette,in, United States, department of animal sciences,purdue university,west lafayette,in, United States, department of animal sciences,purdue university,west lafayette,in, United States, regenerative medicine program,ottawa hospital research institute,ottawa,on, Canada, program in gene function and expression,university of massachusetts medical school,worcester,ma, United States, department of molecular biology,university of texas southwestern medical center,dallas,tx, United States, regenerative medicine program,ottawa hospital research institute,ottawa,on, Canada, department of animal sciences,purdue university,west lafayette,in,united states,purdue university center for cancer research,purdue university,west lafayette,in, United States
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Authors
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