PMID- 37108182
OWN - NLM
STAT- MEDLINE
DCOM- 20230501
LR  - 20230501
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 8
DP  - 2023 Apr 10
TI  - Selective Hepatic Cbs Knockout Aggravates Liver Damage, Endothelial Dysfunction 
      and ROS Stress in Mice Fed a Western Diet.
LID - 10.3390/ijms24087019 [doi]
LID - 7019
AB  - Cystathionine-beta-synthase (CBS) is highly expressed in the liver, and deficiencies 
      in Cbs lead to hyperhomocysteinemia (HHCy) and disturbed production of 
      antioxidants such as hydrogen sulfide. We therefore hypothesized that 
      liver-specific Cbs deficient (LiCKO) mice would be particularly susceptible to 
      the development of non-alcoholic fatty liver disease (NAFLD). NAFLD was induced 
      by a high-fat high-cholesterol (HFC) diet; LiCKO and controls were split into 
      eight groups based on genotype (con, LiCKO), diet (normal diet, HFC), and diet 
      duration (12 weeks, 20 weeks). LiCKO mice displayed intermediate to severe HHCy. 
      Plasma H(2)O(2) was increased by HFC, and further aggravated in LiCKO. LiCKO mice 
      fed an HFC diet had heavier livers, increased lipid peroxidation, elevated ALAT, 
      aggravated hepatic steatosis, and inflammation. LiCKO mice showed decreased 
      L-carnitine in the liver, but this did not result in impaired fatty acid 
      oxidation. Moreover, HFC-fed LiCKO mice demonstrated vascular and renal 
      endothelial dysfunction. Liver and endothelial damage correlated significantly 
      with systemic ROS status. In conclusion, this study demonstrates an important 
      role for CBS in the liver in the development of NAFLD, which is most probably 
      mediated through impaired defense against oxidative stress.
FAU - Lambooy, Sebastiaan
AU  - Lambooy S
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, 9713GZ Groningen, The Netherlands.
FAU - Heida, Andries
AU  - Heida A
AUID- ORCID: 0000-0002-1316-9513
AD  - Department of Pediatrics, University Medical Center Groningen, University of 
      Groningen, 9713GZ Groningen, The Netherlands.
FAU - Joschko, Christian
AU  - Joschko C
AUID- ORCID: 0000-0003-2267-5108
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, 9713GZ Groningen, The Netherlands.
FAU - Nakladal, Dalibor
AU  - Nakladal D
AUID- ORCID: 0000-0003-0900-0130
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, 9713GZ Groningen, The Netherlands.
FAU - van Buiten, Azuwerus
AU  - van Buiten A
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, 9713GZ Groningen, The Netherlands.
FAU - Kloosterhuis, Niels
AU  - Kloosterhuis N
AD  - Department of Pediatrics, University Medical Center Groningen, University of 
      Groningen, 9713GZ Groningen, The Netherlands.
FAU - Huijkman, Nicolette
AU  - Huijkman N
AD  - Department of Pediatrics, University Medical Center Groningen, University of 
      Groningen, 9713GZ Groningen, The Netherlands.
FAU - Gerding, Albert
AU  - Gerding A
AD  - Department of Laboratory Medicine, University Medical Center Groningen, 
      University of Groningen, 9713GZ Groningen, The Netherlands.
FAU - van de Sluis, Bart
AU  - van de Sluis B
AUID- ORCID: 0000-0003-3039-4365
AD  - Department of Pediatrics, University Medical Center Groningen, University of 
      Groningen, 9713GZ Groningen, The Netherlands.
FAU - Henning, Robert
AU  - Henning R
AUID- ORCID: 0000-0002-5135-4621
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, 9713GZ Groningen, The Netherlands.
FAU - Deelman, Leo
AU  - Deelman L
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, 9713GZ Groningen, The Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20230410
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Reactive Oxygen Species)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Non-alcoholic Fatty Liver Disease/genetics
MH  - Reactive Oxygen Species
MH  - Diet, Western/adverse effects
MH  - Hydrogen Peroxide
MH  - Mice, Knockout
MH  - Liver
MH  - *Hyperhomocysteinemia
MH  - Cystathionine beta-Synthase/genetics
MH  - Diet, High-Fat/adverse effects
MH  - Mice, Inbred C57BL
MH  - Disease Models, Animal
PMC - PMC10138434
OTO - NOTNLM
OT  - NAFLD
OT  - cystathionine-beta-synthase
OT  - high-fat diet
OT  - hydrogen sulfide
OT  - hyperhomocysteinemia
OT  - knockout mice
OT  - liver damage
OT  - reactive oxygen species
COIS- The authors declare no conflict of interest.
EDAT- 2023/04/28 06:41
MHDA- 2023/05/01 06:41
PMCR- 2023/04/10
CRDT- 2023/04/28 01:25
PHST- 2023/03/14 00:00 [received]
PHST- 2023/04/07 00:00 [revised]
PHST- 2023/04/08 00:00 [accepted]
PHST- 2023/05/01 06:41 [medline]
PHST- 2023/04/28 06:41 [pubmed]
PHST- 2023/04/28 01:25 [entrez]
PHST- 2023/04/10 00:00 [pmc-release]
AID - ijms24087019 [pii]
AID - ijms-24-07019 [pii]
AID - 10.3390/ijms24087019 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Apr 10;24(8):7019. doi: 10.3390/ijms24087019.