J Cancer 2020; 11(19):5536-5546. doi:10.7150/jca.48495 This issue Cite

Research Paper

Reduction of Polyunsaturated Fatty Acids with Tumor Progression in a Lean Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma Mouse Model

Elizabeth M Vlock1,2, Shilpa Karanjit1, Geoffrey Talmon3, Paraskevi A Farazi1,2✉

1. Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA.
2. Nebraska Center for the Prevention of Obesity Diseases through Dietary Molecules, College of Education and Human Sciences, University of Nebraska Lincoln, Lincoln, NE, USA.
3. Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.

Citation:
Vlock EM, Karanjit S, Talmon G, Farazi PA. Reduction of Polyunsaturated Fatty Acids with Tumor Progression in a Lean Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma Mouse Model. J Cancer 2020; 11(19):5536-5546. doi:10.7150/jca.48495. https://www.jcancer.org/v11p5536.htm
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Abstract

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. While obesity and diabetes are the hallmarks of NAFLD, it also develops in lean individuals in the absence of metabolic syndrome, with a prevalence of 7 percent in the U.S. and 25-30 percent in some Asian countries. NAFLD represents the spectrum of liver disease, starting with excess liver fat accumulation (NAFL) that can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and ultimately hepatocellular carcinoma (HCC). To date, the pathogenesis of lean NASH-HCC is poorly understood and a mouse model is lacking. We aimed to develop a mouse model of lean NASH-HCC using a choline deficient and high trans-fat/sucrose/cholesterol diet to enable better understanding of its molecular pathogenesis.

Methods: C57BL/6N mice were fed this diet starting at 4 weeks of age for 52 weeks and were compared to mice fed an isocaloric low fat control diet for the same duration. C57BL/6N mice were chosen instead of the C57BL/6J mice due to the high susceptibility of C57BL/6J mice to diet-induced obesity. The plasma and tumor fatty acid profile of these mice was also investigated.

Results: Nearly 61% of the mice developed lean NASH-HCC. These mice showed reduction of plasma polyunsaturated fatty acids (PUFAs) (linolenic acids (α and γ, ω-3 and ω-6, respectively), eicosapentanoic acid (ω-3), docosahexanoic acid (ω-3), and linoleic acid (ω-6)) and increasing levels over time in mice with pre-malignant lesions.

Conclusions: We developed a novel high penetrance diet-induced lean NASH-HCC mouse model. Plasma PUFA levels were reduced with tumor progression in parallel with reduced expression of genes controlling desaturase expression suggesting their potential use as biomarkers for lean NASH-HCC progression as well as chemopreventive molecules.

Keywords: liver cancer, non-alcoholic fatty liver disease, unhealthy diet, sugar, fat


Citation styles

APA
Vlock, E.M., Karanjit, S., Talmon, G., Farazi, P.A. (2020). Reduction of Polyunsaturated Fatty Acids with Tumor Progression in a Lean Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma Mouse Model. Journal of Cancer, 11(19), 5536-5546. https://doi.org/10.7150/jca.48495.

ACS
Vlock, E.M.; Karanjit, S.; Talmon, G.; Farazi, P.A. Reduction of Polyunsaturated Fatty Acids with Tumor Progression in a Lean Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma Mouse Model. J. Cancer 2020, 11 (19), 5536-5546. DOI: 10.7150/jca.48495.

NLM
Vlock EM, Karanjit S, Talmon G, Farazi PA. Reduction of Polyunsaturated Fatty Acids with Tumor Progression in a Lean Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma Mouse Model. J Cancer 2020; 11(19):5536-5546. doi:10.7150/jca.48495. https://www.jcancer.org/v11p5536.htm

CSE
Vlock EM, Karanjit S, Talmon G, Farazi PA. 2020. Reduction of Polyunsaturated Fatty Acids with Tumor Progression in a Lean Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma Mouse Model. J Cancer. 11(19):5536-5546.

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