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The American lifestyle-induced obesity syndrome diet in male and female rodents recapitulates the clinical and transcriptomic features of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Harris, SE; Poolman, TM; Arvaniti, A; Cox, RD; Gathercole, LL; Tomlinson, JW; (2020) The American lifestyle-induced obesity syndrome diet in male and female rodents recapitulates the clinical and transcriptomic features of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. American Journal of Physiology - Gastrointestinal and Liver Physiology , 319 (3) G345-G360. 10.1152/ajpgi.00055.2020. Green open access

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Abstract

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the progression to nonalcoholic steatohepatitis (NASH) and increased risk of hepatocellular carcinoma remain poorly understood. Additionally, there is increasing recognition of the extrahepatic manifestations associated with NAFLD and NASH. We demonstrate that intervention with the American lifestyle-induced obesity syndrome (ALIOS) diet in male and female mice recapitulates many of the clinical and transcriptomic features of human NAFLD and NASH. Male and female C57BL/6N mice were fed either normal chow (NC) or ALIOS from 11 to 52 wk and underwent comprehensive metabolic analysis throughout the duration of the study. From 26 wk, ALIOS-fed mice developed features of hepatic steatosis, inflammation, and fibrosis. ALIOS-fed mice also had an increased incidence of hepatic tumors at 52 wk compared with those fed NC. Hepatic transcriptomic analysis revealed alterations in multiple genes associated with inflammation and tissue repair in ALIOS-fed mice. Ingenuity Pathway Analysis confirmed dysregulation of metabolic pathways as well as those associated with liver disease and cancer. In parallel the development of a robust hepatic phenotype, ALIOS-fed mice displayed many of the extrahepatic manifestations of NAFLD, including hyperlipidemia, increased fat mass, sarcopenia, and insulin resistance. The ALIOS diet in mice recapitulates many of the clinical features of NAFLD and, therefore, represents a robust and reproducible model for investigating the pathogenesis of NAFLD and its progression.NEW & NOTEWORTHY Nonalcoholic fatty liver disease (NAFLD) affects 30% of the general population and can progress to nonalcoholic steatohepatitis (NASH) and potentially hepatocellular carcinoma. Preclinical models rely on mouse models that often display hepatic characteristics of NAFLD but rarely progress to NASH and seldom depict the multisystem effects of the disease. We have conducted comprehensive metabolic analysis of both male and female mice consuming a Western diet of trans fats and sugar, focusing on both their hepatic phenotype and extrahepatic manifestations.

Type: Article
Title: The American lifestyle-induced obesity syndrome diet in male and female rodents recapitulates the clinical and transcriptomic features of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1152/ajpgi.00055.2020
Publisher version: http://dx.doi.org/10.1152/ajpgi.00055.2020
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: diet, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, transcriptome
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10108588
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