PMID- 34900535
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211215
IS  - 2211-3835 (Print)
IS  - 2211-3843 (Electronic)
IS  - 2211-3835 (Linking)
VI  - 11
IP  - 11
DP  - 2021 Nov
TI  - Discovery of a potent FKBP38 agonist that ameliorates HFD-induced hyperlipidemia 
      via mTOR/P70S6K/SREBPs pathway.
PG  - 3542-3552
LID - 10.1016/j.apsb.2021.03.031 [doi]
AB  - 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 lipogenesis. 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 flavonoid, 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.
CI  - (c) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, 
      Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
FAU - Xiao, Ping-Ting
AU  - Xiao PT
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 
      Nanjing 210009, China.
FAU - Xie, Zhi-Shen
AU  - Xie ZS
AD  - Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, 
      Zhengzhou 450046, China.
FAU - Kuang, Yu-Jia
AU  - Kuang YJ
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 
      Nanjing 210009, China.
FAU - Liu, Shi-Yu
AU  - Liu SY
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 
      Nanjing 210009, China.
FAU - Zeng, Chun
AU  - Zeng C
AD  - Departments of Pediatrics and Cellular & Molecular Medicine, Pediatric Diabetes 
      Research Center and Institute for Genomic Medicine, University of California, San 
      Diego, La Jolla, CA 92093, USA.
FAU - Li, Ping
AU  - Li P
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 
      Nanjing 210009, China.
FAU - Liu, E-Hu
AU  - Liu EH
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 
      Nanjing 210009, China.
LA  - eng
PT  - Journal Article
DEP - 20210322
PL  - Netherlands
TA  - Acta Pharm Sin B
JT  - Acta pharmaceutica Sinica. B
JID - 101600560
PMC - PMC8642436
OTO - NOTNLM
OT  - 3,5,6,7,8,3',4'-heptamethoxyflavone
OT  - FKBP38
OT  - Hyperlipidemia
OT  - SREBP
OT  - mTOR
COIS- The authors have no conflicts of interest to declare.
EDAT- 2021/12/14 06:00
MHDA- 2021/12/14 06:01
PMCR- 2021/03/22
CRDT- 2021/12/13 18:05
PHST- 2020/12/21 00:00 [received]
PHST- 2021/01/29 00:00 [revised]
PHST- 2021/02/10 00:00 [accepted]
PHST- 2021/12/13 18:05 [entrez]
PHST- 2021/12/14 06:00 [pubmed]
PHST- 2021/12/14 06:01 [medline]
PHST- 2021/03/22 00:00 [pmc-release]
AID - S2211-3835(21)00103-9 [pii]
AID - 10.1016/j.apsb.2021.03.031 [doi]
PST - ppublish
SO  - Acta Pharm Sin B. 2021 Nov;11(11):3542-3552. doi: 10.1016/j.apsb.2021.03.031. 
      Epub 2021 Mar 22.