PMID- 37657642
OWN - NLM
STAT- Publisher
LR  - 20231011
IS  - 1873-4847 (Electronic)
IS  - 0955-2863 (Linking)
VI  - 121
DP  - 2023 Nov
TI  - Maternal protein deficiency impairs peroxisome biogenesis and leads to oxidative 
      stress and ferroptosis in liver of fetal growth restriction offspring.
PG  - 109432
LID - S0955-2863(23)00165-1 [pii]
LID - 10.1016/j.jnutbio.2023.109432 [doi]
AB  - Maternal protein malnutrition leads to liver dysfunction and increases 
      susceptibility to nonalcoholic fatty liver disease in adult fetal growth 
      restriction (FGR) offspring, yet the underlying mechanism remains unknown. 
      Peroxisomes play vital roles in fatty acid beta-oxidation (FAO) and detoxification 
      of reactive oxygen species (ROS). Using a well-defined rat model, the peroxins 
      (PEXs), fatty acid metabolic enzymes, and oxidase stress regulators were 
      investigated in the liver of FGR offspring. The results revealed that PEX3, 11b, 
      14, and 19 were obviously reduced in the fetal liver and lasted to adulthood, 
      suggesting a decrease in the biogenesis and division of peroxisomes. FA 
      metabolism enzymes and ferroptosis regulators were deregulated. To further 
      investigate this association, small interfering RNA was employed to achieve 
      knockdown (KD) of PEX14 in BRL cells (a rat hepatocyte line). PEX14 KD led to 
      dysregulation of PEXs and long-chain FAs accumulation. PEX14 deficiency caused 
      ROS accumulation and lipid peroxidation, finally induced regulated cell death 
      (including apoptosis, autophagy, and ferroptosis). Double knock down (DKD) of 
      PEX14 and fatty acyl-CoA reductase 1 (FAR1) revealed that PEX14 KD-induced 
      ferroptosis was related with enhanced FAR1 level. DKD of PEX14 and Atg5 further 
      confirmed that PEX14 KD-induced cell death was partly autophagy-dependent. 
      Overall, these data demonstrate a vital role for PEX14 in maintaining peroxisome 
      function and liver physiology, and suggest that hepatocyte peroxisome defects 
      partly explain liver dysplasia and lipid metabolism disorders in fetal original 
      liver disease.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Guo, Yanyan
AU  - Guo Y
AD  - Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical 
      University, Shenyang, PR China.
FAU - Zhou, Pei
AU  - Zhou P
AD  - Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical 
      University, Shenyang, PR China.
FAU - Qiao, Lei
AU  - Qiao L
AD  - Department of General Surgery, Shengjing Hospital of China Medical University, 
      Shenyang, PR China.
FAU - Guan, Hongbo
AU  - Guan H
AD  - Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical 
      University, Shenyang, PR China.
FAU - Gou, Jian
AU  - Gou J
AD  - Department of Nutrition, Shengjing Hospital of China Medical University, 
      Shenyang, PR China. Electronic address: gouj@sj-hospital.org.
FAU - Liu, Xiaomei
AU  - Liu X
AD  - Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical 
      University, Shenyang, PR China. Electronic address: liuxm@cmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230830
PL  - United States
TA  - J Nutr Biochem
JT  - The Journal of nutritional biochemistry
JID - 9010081
SB  - IM
OTO - NOTNLM
OT  - FGR
OT  - Peroxisome
OT  - ferroptosis
OT  - liver
OT  - oxidative stress
EDAT- 2023/09/02 05:42
MHDA- 2023/09/02 05:42
CRDT- 2023/09/01 19:24
PHST- 2023/05/25 00:00 [received]
PHST- 2023/07/28 00:00 [revised]
PHST- 2023/08/23 00:00 [accepted]
PHST- 2023/09/02 05:42 [pubmed]
PHST- 2023/09/02 05:42 [medline]
PHST- 2023/09/01 19:24 [entrez]
AID - S0955-2863(23)00165-1 [pii]
AID - 10.1016/j.jnutbio.2023.109432 [doi]
PST - ppublish
SO  - J Nutr Biochem. 2023 Nov;121:109432. doi: 10.1016/j.jnutbio.2023.109432. Epub 
      2023 Aug 30.