Portosystemic shunting prevents hepatocellular carcinoma in non-alcoholic fatty liver disease mouse models.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
01
06
2023
accepted:
09
12
2023
medline:
2
1
2024
pubmed:
2
1
2024
entrez:
29
12
2023
Statut:
epublish
Résumé
Non-alcoholic fatty liver disease (NAFLD) is one of the leading cause of hepatocellular carcinoma (HCC). This association is supported by the translocation of bacteria products into the portal system, which acts on the liver through the gut-liver axis. We hypothesize that portosystemic shunting can disrupt this relationship, and prevent NAFLD-associated HCC. HCC carcinogenesis was tested in C57BL/6 mice fed a high-fat high-sucrose diet (HFD) and injected with diethylnitrosamine (DEN) at two weeks of age, and in double transgenic LAP-tTA and TRE-MYC (LAP-Myc) mice fed a methionine-choline-deficient diet. Portosystemic shunts were established by transposing the spleen to the sub-cutaneous tissue at eight weeks of age. Spleen transposition led to a consistent deviation of part of the portal flow and a significant decrease in portal pressure. It was associated with a decrease in the number of HCC in both models. This effect was supported by the presence of less severe liver steatosis after 40 weeks, and lower expression levels of liver fatty acid synthase. Also, shunted mice exhibited lower liver oxygen levels, a key factor in preventing HCC as confirmed by the development of less HCCs in mice with hepatic artery ligation. The present data show that portosystemic shunting prevents NAFLD-associated HCC, utilizing two independent mouse models. This effect is supported by the development of less steatosis, and a restored liver oxygen level. Portal pressure modulation and shunting deserve further exploration as potential prevention/treatment options for NAFLD and HCC.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Non-alcoholic fatty liver disease (NAFLD) is one of the leading cause of hepatocellular carcinoma (HCC). This association is supported by the translocation of bacteria products into the portal system, which acts on the liver through the gut-liver axis. We hypothesize that portosystemic shunting can disrupt this relationship, and prevent NAFLD-associated HCC.
METHODS
METHODS
HCC carcinogenesis was tested in C57BL/6 mice fed a high-fat high-sucrose diet (HFD) and injected with diethylnitrosamine (DEN) at two weeks of age, and in double transgenic LAP-tTA and TRE-MYC (LAP-Myc) mice fed a methionine-choline-deficient diet. Portosystemic shunts were established by transposing the spleen to the sub-cutaneous tissue at eight weeks of age.
RESULTS
RESULTS
Spleen transposition led to a consistent deviation of part of the portal flow and a significant decrease in portal pressure. It was associated with a decrease in the number of HCC in both models. This effect was supported by the presence of less severe liver steatosis after 40 weeks, and lower expression levels of liver fatty acid synthase. Also, shunted mice exhibited lower liver oxygen levels, a key factor in preventing HCC as confirmed by the development of less HCCs in mice with hepatic artery ligation.
CONCLUSIONS
CONCLUSIONS
The present data show that portosystemic shunting prevents NAFLD-associated HCC, utilizing two independent mouse models. This effect is supported by the development of less steatosis, and a restored liver oxygen level. Portal pressure modulation and shunting deserve further exploration as potential prevention/treatment options for NAFLD and HCC.
Identifiants
pubmed: 38157359
doi: 10.1371/journal.pone.0296265
pii: PONE-D-23-16913
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0296265Informations de copyright
Copyright: © 2023 Peloso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.