PMID- 36716821
OWN - NLM
STAT- MEDLINE
DCOM- 20230329
LR  - 20230404
IS  - 1539-7262 (Electronic)
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 64
IP  - 3
DP  - 2023 Mar
TI  - Phosphoethanolamine cytidylyltransferase ameliorates mitochondrial function and 
      apoptosis in hepatocytes in T2DM in vitro.
PG  - 100337
LID - S0022-2275(23)00010-X [pii]
LID - 10.1016/j.jlr.2023.100337 [doi]
LID - 100337
AB  - Liver function indicators are often impaired in patients with type 2 diabetes 
      mellitus (T2DM), who present higher concentrations of aspartate aminotransferase, 
      alanine aminotransferase, and gamma-glutamyl transferase than individuals without 
      diabetes. However, the mechanism of liver injury in patients with T2DM has not 
      been clearly elucidated. In this study, we performed a lipidomics analysis on the 
      liver of T2DM mice, and we found that phosphatidylethanolamine (PE) levels were 
      low in T2DM, along with an increase in diglyceride, which may be due to a 
      decrease in the levels of phosphoethanolamine cytidylyltransferase (Pcyt2), thus 
      likely affecting the de novo synthesis of PE. The phosphatidylserine 
      decarboxylase pathway did not change significantly in the T2DM model, although 
      both pathways are critical sources of PE. Supplementation with CDP-ethanolamine 
      (CDP-etn) to increase the production of PE from the CDP-etn pathway reversed high 
      glucose and FFA (HG&FFA)-induced mitochondrial damage including increased 
      apoptosis, decreased ATP synthesis, decreased mitochondrial membrane potential, 
      and increased reactive oxygen species, whereas supplementation with 
      lysophosphatidylethanolamine, which can increase PE production in the 
      phosphatidylserine decarboxylase pathway, did not. Additionally, we found that 
      overexpression of PCYT2 significantly ameliorated ATP synthesis and abnormal 
      mitochondrial morphology induced by HG&FFA. Finally, the BAX/Bcl-2/caspase3 
      apoptosis pathway was activated in hepatocytes of the T2DM model, which could 
      also be reversed by CDP-etn supplements and PCYT2 overexpression. In summary, in 
      the liver of T2DM mice, Pcyt2 reduction may lead to a decrease in the levels of 
      PE, whereas CDP-etn supplementation and PCYT2 overexpression ameliorate partial 
      mitochondrial function and apoptosis in HG&FFA-stimulated L02 cells.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Xu, Hu
AU  - Xu H
AD  - Basic Medical College, Anhui Medical University, Hefei, China.
FAU - Li, Weizu
AU  - Li W
AD  - Basic Medical College, Anhui Medical University, Hefei, China.
FAU - Huang, Lei
AU  - Huang L
AD  - Basic Medical College, Anhui Medical University, Hefei, China.
FAU - He, Xinyu
AU  - He X
AD  - Basic Medical College, Anhui Medical University, Hefei, China.
FAU - Xu, Bei
AU  - Xu B
AD  - Basic Medical College, Anhui Medical University, Hefei, China.
FAU - He, Xueqing
AU  - He X
AD  - Basic Medical College, Anhui Medical University, Hefei, China.
FAU - Chen, Wentong
AU  - Chen W
AD  - Basic Medical College, Anhui Medical University, Hefei, China.
FAU - Wang, Yaoxing
AU  - Wang Y
AD  - Basic Medical College, Anhui Medical University, Hefei, China.
FAU - Xu, Wenjun
AU  - Xu W
AD  - Basic Medical College, Anhui Medical University, Hefei, China.
FAU - Wang, Sheng
AU  - Wang S
AD  - Center for Scientific Research, Anhui Medical University, Hefei, China.
FAU - Kong, Qin
AU  - Kong Q
AD  - Basic Medical College, Anhui Medical University, Hefei, China.
FAU - Xu, Youzhi
AU  - Xu Y
AD  - Basic Medical College, Anhui Medical University, Hefei, China. Electronic 
      address: xuyouzhi@ahmu.edu.cn.
FAU - Lu, Wenjie
AU  - Lu W
AD  - Basic Medical College, Anhui Medical University, Hefei, China. Electronic 
      address: wenjie63136@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230128
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 78A2BX7AEU (phosphorylethanolamine)
RN  - 0 (Phosphatidylethanolamines)
RN  - EC 2.7.7.- (RNA Nucleotidyltransferases)
RN  - 0 (Ethanolamines)
RN  - 3036-18-8 (CDP ethanolamine)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Phosphatidylethanolamines/metabolism
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - RNA Nucleotidyltransferases/metabolism
MH  - Ethanolamines/pharmacology/metabolism
MH  - Hepatocytes/metabolism
MH  - Mitochondria/metabolism
MH  - Apoptosis
MH  - Adenosine Triphosphate/metabolism
PMC - PMC10033998
OTO - NOTNLM
OT  - ATP synthesis
OT  - cytidine-5'-diphosphate-ethanolamine pathway
OT  - high glucose and free fatty acids
OT  - lipidomics
OT  - liver
OT  - mitochondria
OT  - phosphatidylethanolamine
OT  - phosphatidylserine decarboxylase pathway
OT  - phospholipids
OT  - type 2 diabetes mellitus
COIS- Conflict of iInterest The authors declare that they have no conflicts of interest 
      with the contents of this article.
EDAT- 2023/01/31 06:00
MHDA- 2023/03/29 06:05
PMCR- 2023/01/28
CRDT- 2023/01/30 19:24
PHST- 2022/02/08 00:00 [received]
PHST- 2022/12/22 00:00 [revised]
PHST- 2022/12/22 00:00 [accepted]
PHST- 2023/03/29 06:05 [medline]
PHST- 2023/01/31 06:00 [pubmed]
PHST- 2023/01/30 19:24 [entrez]
PHST- 2023/01/28 00:00 [pmc-release]
AID - S0022-2275(23)00010-X [pii]
AID - 100337 [pii]
AID - 10.1016/j.jlr.2023.100337 [doi]
PST - ppublish
SO  - J Lipid Res. 2023 Mar;64(3):100337. doi: 10.1016/j.jlr.2023.100337. Epub 2023 Jan 
      28.