Articles producció científica> Medicina i Cirurgia

HNF4a-deficient fatty liver provides a permissive environment for sex-independent hepatocellular carcinoma

  • Identification data

    Identifier: imarina:6389702
    Authors:
    Fekry BRibas-Latre ABaumgartner CMohamed AKolonin MSladek FYounes MEckel-Mahan K
    Abstract:
    ©©2019 American Association for Cancer Research. The incidence of hepatocellular carcinoma (HCC) is on the rise worldwide. Although the incidence of HCC in males is considerably higher than in females, the projected rates of HCC incidence are increasing for both sexes. A recently appreciated risk factor for HCC is the growing problem of nonalcoholic fatty liver disease, which is usually associated with obesity and the metabolic syndrome. In this study, we showed that under conditions of fatty liver, female mice were more likely to develop HCC than expected from previous models. Using an inducible knockout model of the tumor-suppressive isoform of hepatocyte nuclear factor 4 alpha (P1-HNF4α) in the liver in combination with prolonged high fat (HF) diet, we found that HCC developed equally in male and female mice as early as 38 weeks of age. Similar sex-independent HCC occurred in the STAM model of mice, in which severe hyperglycemia and HF feeding results in rapid hepatic lipid deposition, fibrosis, and ultimately HCC. In both sexes, reduced P1-HNF4α activity, which also occurs under chronic HF diet feeding, increased hepatic lipid deposition and produced a greatly augmented circadian rhythm in IL6, a factor previously linked with higher HCC incidence in males. Loss of HNF4α combined with HF feeding induced epithelial–mesenchymal transition in an IL6-dependent manner. Collectively, these data provide a mechanism-based working hypothesis that could explain the rising incidence of aggressive HCC. Significance: This study provides a mechanism for the growing incidence of hepatocellular carcinoma in both men and women, which is linked to nonalcoholic fatty liver disease.
  • Others:

    Author, as appears in the article.: Fekry B; Ribas-Latre A; Baumgartner C; Mohamed A; Kolonin M; Sladek F; Younes M; Eckel-Mahan K
    Department: Medicina i Cirurgia
    URV's Author/s: Ribas Latre, Aleix
    Abstract: ©©2019 American Association for Cancer Research. The incidence of hepatocellular carcinoma (HCC) is on the rise worldwide. Although the incidence of HCC in males is considerably higher than in females, the projected rates of HCC incidence are increasing for both sexes. A recently appreciated risk factor for HCC is the growing problem of nonalcoholic fatty liver disease, which is usually associated with obesity and the metabolic syndrome. In this study, we showed that under conditions of fatty liver, female mice were more likely to develop HCC than expected from previous models. Using an inducible knockout model of the tumor-suppressive isoform of hepatocyte nuclear factor 4 alpha (P1-HNF4α) in the liver in combination with prolonged high fat (HF) diet, we found that HCC developed equally in male and female mice as early as 38 weeks of age. Similar sex-independent HCC occurred in the STAM model of mice, in which severe hyperglycemia and HF feeding results in rapid hepatic lipid deposition, fibrosis, and ultimately HCC. In both sexes, reduced P1-HNF4α activity, which also occurs under chronic HF diet feeding, increased hepatic lipid deposition and produced a greatly augmented circadian rhythm in IL6, a factor previously linked with higher HCC incidence in males. Loss of HNF4α combined with HF feeding induced epithelial–mesenchymal transition in an IL6-dependent manner. Collectively, these data provide a mechanism-based working hypothesis that could explain the rising incidence of aggressive HCC. Significance: This study provides a mechanism for the growing incidence of hepatocellular carcinoma in both men and women, which is linked to nonalcoholic fatty liver disease.
    Thematic Areas: Astronomia / física Biotecnología Cancer research Ciências biológicas i Ciências biológicas ii Ciências biológicas iii Farmacia General medicine Interdisciplinar Medicina i Medicina ii Medicina iii Medicina veterinaria Odontología Oncology Química Saúde coletiva
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: aleix.ribas@urv.cat
    Record's date: 2023-02-19
    Papper version: info:eu-repo/semantics/acceptedVersion
    Link to the original source: https://aacrjournals.org/cancerres/article/79/22/5860/638347/HNF4-Deficient-Fatty-Liver-Provides-a-Permissive
    Papper original source: Cancer Research. 79 (22): 5860-5873
    APA: Fekry B; Ribas-Latre A; Baumgartner C; Mohamed A; Kolonin M; Sladek F; Younes M; Eckel-Mahan K (2019). HNF4a-deficient fatty liver provides a permissive environment for sex-independent hepatocellular carcinoma. Cancer Research, 79(22), 5860-5873. DOI: 10.1158/0008-5472.CAN-19-1277
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Article's DOI: 10.1158/0008-5472.CAN-19-1277
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2019
    Publication Type: Journal Publications
  • Keywords:

    Cancer Research,Oncology
    Astronomia / física
    Biotecnología
    Cancer research
    Ciências biológicas i
    Ciências biológicas ii
    Ciências biológicas iii
    Farmacia
    General medicine
    Interdisciplinar
    Medicina i
    Medicina ii
    Medicina iii
    Medicina veterinaria
    Odontología
    Oncology
    Química
    Saúde coletiva
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