Περίληψη:
The prevalence of obesity and non-alcoholic fatty liver disease (NAFLD)
associated hepatocellular carcinoma (HCC) is rising, even in the absence
of cirrhosis. We aimed to develop a murine model that would facilitate
further understanding of NAFLD-HCC pathogenesis. A total of 144 C3H/He
mice were fed either control or American lifestyle (ALIOS) diet, with or
without interventions, for up to 48 weeks of age. Gross, liver
histology, immunohistochemistry (IHC) and RNA-sequencing data were
interpreted alongside human datasets. The ALIOS diet promoted obesity,
elevated liver weight, impaired glucose tolerance, non-alcoholic fatty
liver disease (NAFLD) and spontaneous HCC. Liver weight, fasting blood
glucose, steatosis, lobular inflammation and lipogranulomas were
associated with development of HCC, as were markers of hepatocyte
proliferation and DNA damage. An antioxidant diminished cellular injury,
fibrosis and DNA damage, but not lobular inflammation, lipogranulomas,
proliferation and HCC development. An acquired CD44 phenotype in
macrophages was associated with type 2 diabetes and NAFLD-HCC. In this
diet induced NASH and HCC (DINAH) model, key features of obesity
associated NAFLD-HCC have been reproduced, highlighting roles for
hepatic steatosis and proliferation, with the acquisition of lobular
inflammation and CD44 positive macrophages in the development of
HCC-even in the absence of progressive injury and fibrosis.
Συγγραφείς:
Zaki, Marco Youssef William
Mahdi, Ahmed Khairallah
Patman,
Gillian Lucinda
Whitehead, Anna
Mauricio, Joao Pais
McCain,
Misti Vanette
Televantou, Despina
Abou-Beih, Sameh and
Ramon-Gil, Erik
Watson, Robyn
Cox, Charlotte
Leslie, Jack
and Wilson, Caroline
Govaere, Olivier
Lunec, John
Mann,
Derek Austin
Nakjang, Sirintra
Oakley, Fiona
Shukla, Ruchi
and Anstee, Quentin Mark
Tiniakos, Dina
Reeves, Helen Louise
