PMID- 29453982
OWN - NLM
STAT- MEDLINE
DCOM- 20180509
LR  - 20180509
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 497
IP  - 2
DP  - 2018 Mar 4
TI  - Glucagon-like peptide-1 contributes to increases ABCA1 expression by 
      downregulating miR-758 to regulate cholesterol homeostasis.
PG  - 652-658
LID - S0006-291X(18)30357-7 [pii]
LID - 10.1016/j.bbrc.2018.02.126 [doi]
AB  - Abnormal regulation of lipid metabolism is associated with type 2 diabetes 
      mellitus (T2DM). GLP-1 as a new treatment for T2DM, has unique effects in 
      modulating cholesterol homeostasis. However, the mechanism of this effect is 
      largely missing. The aim of this study was to determine the effects of GLP-1 on 
      cholesterol-induced lipotoxicity in hepatocytes and examine the underlying 
      mechanisms. The cell viability was determined, and caspase-3 was used to detect 
      the effects of GLP-1 on cholesterol-induced apoptosis. The alterations of miR-758 
      and ATP-binding cassette transporter A1 (ABCA1) resulting from cholesterol 
      incubation or GLP-1 were detected by qRT-PCR and Western blot assays. 
      Overexpression of miR-758 abrogated the GLP-1-mediated ABCA1 expression, and 
      conversely, down-regulation of miR-758 aggravated GLP-1's action and revealed 
      significant promotion effects. BODIPY-Cholesterol efflux assay revealed that 
      treatment with miR-758 inhibitor significantly enhanced ABCA1-dependent 
      cholesterol efflux, resulting in reduced total cholesterol. Furthermore, Oil red 
      O staining and cholesterol measurement were used to detect lipid accumulation. As 
      a result, cholesterol significantly attenuated cell viability, promoted cell 
      apoptosis, and facilitated lipid accumulation, and these effects were reversed by 
      GLP-1. This study provides evidence that, in HepG2 cells, GLP-1 may affect 
      cholesterol homeostasis by regulating the expression of miR-758 and ABCA1. These 
      data can inform the development of biomarkers for miR-758, and potentially other 
      drugs, on the key pathways of lipid metabolism.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Yao, Yue
AU  - Yao Y
AD  - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin 
      Medical University, Harbin, 150086, China.
FAU - Li, Qiang
AU  - Li Q
AD  - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin 
      Medical University, Harbin, 150086, China. Electronic address: 
      qiangli@hrbmu.edu.cn.
FAU - Gao, Ping
AU  - Gao P
AD  - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin 
      Medical University, Harbin, 150086, China.
FAU - Wang, Wei
AU  - Wang W
AD  - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin 
      Medical University, Harbin, 150086, China.
FAU - Chen, Lili
AU  - Chen L
AD  - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin 
      Medical University, Harbin, 150086, China.
FAU - Zhang, Jinchao
AU  - Zhang J
AD  - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin 
      Medical University, Harbin, 150086, China.
FAU - Xu, Yi
AU  - Xu Y
AD  - Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of 
      Harbin Medical University, Harbin, 150086, China. Electronic address: 
      xuyi@hrbmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180215
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (ABCA1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (MIRN758 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - ATP Binding Cassette Transporter 1/*genetics
MH  - Cholesterol/*metabolism
MH  - Down-Regulation
MH  - *Gene Expression Regulation
MH  - Glucagon-Like Peptide 1/*metabolism
MH  - Hep G2 Cells
MH  - Homeostasis
MH  - Humans
MH  - MicroRNAs/*genetics
MH  - Up-Regulation
OTO - NOTNLM
OT  - ABCA1
OT  - Cholesterol homeostasis
OT  - GLP-1
OT  - miR-758
EDAT- 2018/02/18 06:00
MHDA- 2018/05/10 06:00
CRDT- 2018/02/18 06:00
PHST- 2018/02/10 00:00 [received]
PHST- 2018/02/14 00:00 [accepted]
PHST- 2018/02/18 06:00 [pubmed]
PHST- 2018/05/10 06:00 [medline]
PHST- 2018/02/18 06:00 [entrez]
AID - S0006-291X(18)30357-7 [pii]
AID - 10.1016/j.bbrc.2018.02.126 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Mar 4;497(2):652-658. doi: 
      10.1016/j.bbrc.2018.02.126. Epub 2018 Feb 15.