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Obesity and hepatocellular carcinoma: targeting obesity-related inflammation for chemoprevention of liver carcinogenesis

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Abstract

Obesity and related metabolic abnormalities, including a state of chronic inflammation, increase the risk of hepatocellular carcinoma (HCC). Adipose tissue constitutively expresses the proinflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which are important tumor promoters in inflammation-related carcinogenesis. Dysregulation of TNF-α and IL-6 is associated with the development of steatosis and inflammation within the liver. These cytokines also lie at the core of the association between obesity and insulin resistance, which is a key factor in the development of obesity-related HCC. Here we present a detailed review of the relationship between metabolic abnormalities and the development of HCC, focusing on the role played by inflammation. Drawing from our basic and clinical research, the present report also reviews evidence that targeting metabolic abnormalities, such as attenuation of chronic inflammation and improvement of insulin resistance by either pharmaceutical or nutritional intervention, may be an effective strategy in preventing the development of HCC in obese individuals.

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Acknowledgments

This review was based on studies supported in part by Grants-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan (No. 22790638 to M. S. and No. 21590838 to H. M.) and by Grant-in-Aid for the 3rd Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour, and Welfare of Japan.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan

    Masahito Shimizu & Hisataka Moriwaki

  2. The Tohkai Cytopathology Institute: Cancer Research and Prevention (TCI-CaRP), Gifu, 500-8285, Japan

    Takuji Tanaka

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  1. Masahito Shimizu
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  2. Takuji Tanaka
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  3. Hisataka Moriwaki
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Correspondence to Masahito Shimizu.

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This article is a contribution to the special issue on Inflammation and Cancer - Guest Editor: Takuji Tanaka

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Shimizu, M., Tanaka, T. & Moriwaki, H. Obesity and hepatocellular carcinoma: targeting obesity-related inflammation for chemoprevention of liver carcinogenesis. Semin Immunopathol 35, 191–202 (2013). https://doi.org/10.1007/s00281-012-0336-6

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  • DOI: https://doi.org/10.1007/s00281-012-0336-6

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