PMID- 31828866
OWN - NLM
STAT- MEDLINE
DCOM- 20200730
LR  - 20211204
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Linking)
VI  - 34
IP  - 6
DP  - 2020 Jun
TI  - Scutellarin, a modulator of mTOR, attenuates hepatic insulin resistance by 
      regulating hepatocyte lipid metabolism via SREBP-1c suppression.
PG  - 1455-1466
LID - 10.1002/ptr.6582 [doi]
AB  - High levels of consumption of saturated lipids have been largely associated with 
      the increasing prevalence of metabolic diseases. In particular, saturated fatty 
      acids such as palmitic acid (PA) have been implicated in the development of 
      insulin resistance (IR). Scutellarin (Scu) is one of the effective traditional 
      Chinese medicines considered beneficial for liver diseases and diabetes. In this 
      study, we investigated the effect of Scu on IR and lipid metabolism disorders in 
      vitro and in high fat diet (HFD)-fed mice. In vitro, we found that Scu decreased 
      insulin-dependent lipid accumulation and the mRNA expression of CD36, Fasn, and 
      ACC in PA-treated HepG2 cells. Additionally, Scu upregulated Akt phosphorylation 
      and improved the insulin signalling pathway. Moreover, Scu downregulated 
      mammalian target of rapamycin (mTOR) phosphorylation and the n-SREBP-1c protein 
      level and also reduced lipid accumulation via the mTOR-dependent pathway, as 
      confirmed by the molecular docking of Scu to mTOR. In HFD-fed C57BL/6 mice, Scu 
      improved oral glucose tolerance, pyruvate tolerance and the IR index and also 
      increased the Akt phosphorylation level. Moreover, Scu reduced hepatocyte 
      steatosis, decreased lipid accumulation and triglyceride levels, inhibited mTOR 
      phosphorylation, and decreased the SREBP-1c level in the liver. Taken together, 
      these findings suggest that Scu ameliorates hepatic IR by regulating hepatocyte 
      lipid metabolism via the mTOR-dependent pathway through SREBP-1c suppression.
CI  - (c) 2019 John Wiley & Sons, Ltd.
FAU - Luan, Huiling
AU  - Luan H
AD  - Department of Pharmacology of Chinese Materia Medica, School of Traditional 
      Chinese Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of 
      China.
FAU - Huo, Zhaojiong
AU  - Huo Z
AD  - Department of Pharmacology of Chinese Materia Medica, School of Traditional 
      Chinese Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of 
      China.
FAU - Zhao, Zifeng
AU  - Zhao Z
AD  - Department of Pharmacology of Chinese Materia Medica, School of Traditional 
      Chinese Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of 
      China.
FAU - Zhang, Shoukang
AU  - Zhang S
AD  - Department of Pharmacology of Chinese Materia Medica, School of Traditional 
      Chinese Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of 
      China.
FAU - Huang, Yihai
AU  - Huang Y
AD  - Department of Pharmacology of Chinese Materia Medica, School of Traditional 
      Chinese Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of 
      China.
FAU - Shen, Yanhui
AU  - Shen Y
AD  - Department of Pharmacology of Chinese Materia Medica, School of Traditional 
      Chinese Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of 
      China.
FAU - Wang, Pu
AU  - Wang P
AD  - Department of Pharmacology of Chinese Materia Medica, School of Traditional 
      Chinese Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of 
      China.
FAU - Xi, Junxiao
AU  - Xi J
AD  - Department of Pharmacology of Chinese Materia Medica, School of Traditional 
      Chinese Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of 
      China.
FAU - Liang, Jingyu
AU  - Liang J
AD  - Department of Natural Medicinal Chemistry, School of Traditional Chinese 
      Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
FAU - Wu, Feihua
AU  - Wu F
AUID- ORCID: 0000-0001-5316-5915
AD  - Department of Pharmacology of Chinese Materia Medica, School of Traditional 
      Chinese Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of 
      China.
LA  - eng
GR  - Priority Academic Program Development of Jiangsu Higher Education Institutions/
GR  - KYCX18_0829/Postgraduate Research & Practice Innovation Program of Jiangsu 
      Province/
PT  - Journal Article
DEP - 20191211
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - 0 (Glucuronates)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 16IGP0ML9A (scutellarin)
RN  - 7V515PI7F6 (Apigenin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Apigenin/pharmacology/*therapeutic use
MH  - Cell Culture Techniques
MH  - Glucuronates/pharmacology/*therapeutic use
MH  - Hepatocytes/*metabolism
MH  - Humans
MH  - Lipid Metabolism/*drug effects
MH  - Male
MH  - Mice
MH  - Molecular Docking Simulation/*methods
MH  - Sterol Regulatory Element Binding Protein 1/*metabolism
MH  - TOR Serine-Threonine Kinases/*drug effects
OTO - NOTNLM
OT  - hepatic insulin resistance
OT  - lipid accumulation
OT  - mTOR
OT  - n-SREBP-1c
EDAT- 2019/12/13 06:00
MHDA- 2020/07/31 06:00
CRDT- 2019/12/13 06:00
PHST- 2019/07/28 00:00 [received]
PHST- 2019/11/09 00:00 [revised]
PHST- 2019/11/19 00:00 [accepted]
PHST- 2019/12/13 06:00 [pubmed]
PHST- 2020/07/31 06:00 [medline]
PHST- 2019/12/13 06:00 [entrez]
AID - 10.1002/ptr.6582 [doi]
PST - ppublish
SO  - Phytother Res. 2020 Jun;34(6):1455-1466. doi: 10.1002/ptr.6582. Epub 2019 Dec 11.