PMID- 32771373
OWN - NLM
STAT- MEDLINE
DCOM- 20210726
LR  - 20210726
IS  - 1873-5169 (Electronic)
IS  - 0196-9781 (Linking)
VI  - 133
DP  - 2020 Nov
TI  - Liraglutide ameliorates lipotoxicity-induced inflammation through the mTORC1 
      signalling pathway.
PG  - 170375
LID - S0196-9781(20)30124-8 [pii]
LID - 10.1016/j.peptides.2020.170375 [doi]
AB  - Lipotoxicity has been implicated in many disease processes, and prolonged 
      exposure to high lipid levels often leads to the activation of a variety of 
      abnormal signals, which in turn leads to the induction of inflammation. The aim 
      of our study was to explore the correlation between mammalian target of rapamycin 
      (mTOR) and inflammation by studying high-fat diet (HFD)-induced non-alcoholic 
      fatty liver disease (NAFLD) in rats and palmitate (PA)-induced inflammation 
      (lipotoxicity) in HepG2 cells. In addition, we investigated whether the 
      glucagon-like peptide-1 (GLP-1) analogue liraglutide can protect rats and HepG2 
      cells from lipotoxicity. Our results showed that an HFD and PA significantly 
      increased inflammation by activating the mTORC1 pathway in vitro and in vivo. 
      Treatment with rapamycin (an mTOR inhibitor) inhibited some effects of PA on 
      inflammation. Furthermore, we observed that liraglutide inhibited PA-induced 
      inflammation by inactivating mTORC1 signalling molecules. Overall, our findings 
      demonstrated that mTORC1 signalling pathways were involved primarily in high 
      lipid level-induced inflammation. Importantly, liraglutide may protect against 
      lipotoxicity-induced inflammation by regulating mTORC1-dependent pathways.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Ao, Na
AU  - Ao N
AD  - Department of Endocrinology, the Fourth Affiliated Hospital of China Medical 
      University, Shenyang, China.
FAU - Ma, Zhuoqi
AU  - Ma Z
AD  - Department of Endocrinology, the Fourth Affiliated Hospital of China Medical 
      University, Shenyang, China.
FAU - Yang, Jing
AU  - Yang J
AD  - Department of Endocrinology, the Fourth Affiliated Hospital of China Medical 
      University, Shenyang, China.
FAU - Jin, Shi
AU  - Jin S
AD  - Department of Endocrinology, the Fourth Affiliated Hospital of China Medical 
      University, Shenyang, China.
FAU - Zhang, Keying
AU  - Zhang K
AD  - Department of Endocrinology, the Fifth People's Hospital of Shenyang, Shenyang, 
      China.
FAU - Luo, Enjie
AU  - Luo E
AD  - Department of Pathogen Biology, College of Basic Medical Sciences, China Medical 
      University, Shenyang, China. Electronic address: enjie359@126.com.
FAU - Du, Jian
AU  - Du J
AD  - Department of Endocrinology, the Fourth Affiliated Hospital of China Medical 
      University, Shenyang, China. Electronic address: dujianbox@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200807
PL  - United States
TA  - Peptides
JT  - Peptides
JID - 8008690
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, rat)
RN  - 0 (Palmitates)
RN  - 839I73S42A (Liraglutide)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
SB  - IM
MH  - Animals
MH  - Body Weight/drug effects
MH  - Diet, High-Fat/adverse effects
MH  - Eating/drug effects
MH  - Hep G2 Cells
MH  - Hepatitis/*drug therapy/etiology
MH  - Humans
MH  - Inflammasomes/drug effects/metabolism
MH  - Insulin Resistance
MH  - Liraglutide/*pharmacology
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1/*drug effects/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/pathology
MH  - Palmitates/toxicity
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - Inflammation
OT  - Lipotoxicity
OT  - Liraglutide
OT  - Non-alcoholic fatty liver disease
OT  - mTORC1
EDAT- 2020/08/11 06:00
MHDA- 2021/07/27 06:00
CRDT- 2020/08/11 06:00
PHST- 2020/04/25 00:00 [received]
PHST- 2020/07/16 00:00 [revised]
PHST- 2020/07/17 00:00 [accepted]
PHST- 2020/08/11 06:00 [pubmed]
PHST- 2021/07/27 06:00 [medline]
PHST- 2020/08/11 06:00 [entrez]
AID - S0196-9781(20)30124-8 [pii]
AID - 10.1016/j.peptides.2020.170375 [doi]
PST - ppublish
SO  - Peptides. 2020 Nov;133:170375. doi: 10.1016/j.peptides.2020.170375. Epub 2020 Aug 
      7.