Hepatocellular carcinoma emergence in diabetic mice with non-alcoholic steatohepatitis depends on diet and is delayed in liver exhibiting an active immune response

Mélanie Simoes Eugénio, Muhammad Farooq, Sarah Dion, Christelle Devisme, Céline Raguenes-Nicol, Claire Piquet-Pellorce, Michel Samson, Marie Thérèse Dimanche-Boitrel*, Jacques Le Seyec

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

The increase of the sedentary lifestyle and high-calorie diet have modified the etiological landscape of hepatocellular carcinoma (HCC), with a recrudescence of non-alcoholic fatty liver disease (NAFLD), especially in Western countries. The purpose of our study was to evaluate the impact of high-fat diet feeding on non-alcoholic steatohepatitis (NASH) establishment and HCC development. Streptozotocin-induced diabetic male mice were fed with high-fat-high-cholesterol diet (HFHCD) or high-fat-high-sugar diet (HFHSD) from 1 to 16 weeks. Even if liver tumors appear regardless of the high-fat diet, two distinct physiopathological patterns were evidenced, with much more severe NASH hallmarks (liver injury, inflammation and fibrosis) in diabetic mice fed with HFHCD. The mild hepatic injury, weak inflammation and fibrosis observed in HFHSD were interestingly associated with earlier emergence of more numerous liver tumors. When activated helper and cytotoxic T cells, detected by flow cytometry, infiltrated the liver of HFHCD-fed diabetic mice, a delay in the appearance of tumor nodules and a limitation of their numbers were observed, suggesting that the immune activities partly controlled tumor emergence. These data highlighted two different mouse models of HCC progression in diabetic mice depending on diet, which could be useful to evaluate new therapeutic approaches for HCC by targeting the immune response.

Original languageEnglish
Article number1491
Pages (from-to)1-17
Number of pages17
JournalCancers
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 2020
Externally publishedYes

Keywords

  • Animal study
  • HCC
  • NASH
  • Nutrition

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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