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Scientific article
Open access
English

Portosystemic shunting prevents hepatocellular carcinoma in non-alcoholic fatty liver disease mouse models

Published inPloS one, vol. 18, no. 12, e0296265
Publication date2023
First online date2023-12-29
Abstract

Background and aims: 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: 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: 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: 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.

eng
Keywords
  • Animals
  • Mice
  • Carcinoma, Hepatocellular / pathology
  • Non-alcoholic Fatty Liver Disease / pathology
  • Liver Neoplasms / pathology
  • Mice, Inbred C57BL
  • Liver / metabolism
  • Diet, High-Fat / adverse effects
  • Oxygen / metabolism
  • Disease Models, Animal
Citation (ISO format)
PELOSO, Andréa et al. Portosystemic shunting prevents hepatocellular carcinoma in non-alcoholic fatty liver disease mouse models. In: PloS one, 2023, vol. 18, n° 12, p. e0296265. doi: 10.1371/journal.pone.0296265
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Identifiers
ISSN of the journal1932-6203
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