【摘 要】
：
The mammalian target of rapamycin(mTOR)-sterol regulatory element-binding proteins(SREBPs)signaling promotes lipogenesis.However,mTOR inhibitors also displayed a significant side effect of hyperlipidemia.Thus,it is essential to develop mTOR-specific inhib
【机 构】
：
State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China;Acade
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The mammalian target of rapamycin(mTOR)-sterol regulatory element-binding proteins(SREBPs)signaling promotes lipogenesis.However,mTOR inhibitors also displayed a significant side effect of hyperlipidemia.Thus,it is essential to develop mTOR-specific inhibitors to inhibit lipo-genesis.Here,we screened the endogenous inhibitors of mTOR,and identified that FKBP38 as a vital regulator of lipid metabolism.FKBP38 decreased the lipid content in vitro and in vivo via suppression of the mTOR/P70S6K/SREBPs pathway.3,5,6,7,8,3\',4\'-Heptamethoxyflavone(HMF),a citrus flavo-noid,was found to target FKBP38 to suppress the mTOR/P70S6K/SREBPs pathway,reduce lipid level,and potently ameliorate hyperlipidemia and insulin resistance in high fat diet(HFD)-fed mice.Our findings suggest that pharmacological intervention by targeting FKBP38 to suppress mTOR/P70S6K/SREBPs pathway is a potential therapeutic strategy for hyperlipidemia,and HMF could be a leading compound for development of anti-hyperlipidemia drugs.
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