title: Chemoprevention of obesity-related liver carcinogenesis by using pharmaceutical and nutraceutical agents.
abstract: Obesity and its related metabolic disorders are serious health problems worldwide, and lead to various health-related complications, including cancer. Among human cancers, hepatocellular carcinoma (HCC) is one of the most common malignancies affected by obesity. Therefore, obesity and its related disorders might be a key target for the prevention of HCC. Recently, new research indicates that the molecular abnormalities associated with obesity, including insulin resistance/hyperinsulinemia, chronic inflammation, adipokine imbalance, and oxidative stress, are possible molecular mechanisms underlying the pathogenesis of obesity-related hepatocarcinogenesis. Green tea catechins and branched-chain amino acids, both of which are classified as nutraceutical agents, have been reported to prevent obesity-related HCC development by improving metabolic abnormalities. The administration of acyclic retinoid, a pharmaceutical agent, reduced the incidence of HCC in obese and diabetic mice, and was also associated with improvements in insulin resistance and chronic inflammation. In this article, we review the detailed molecular mechanisms that link obesity to the development of HCC in obese individuals. We also summarize recent evidence from experimental and clinical studies using either nutraceutical or pharmaceutical agents, and suggest that nutraceutical and pharmaceutical approaches targeting metabolic abnormalities might be a promising strategy to prevent the development of obesity-related HCC.
authors.affiliation: Hiroyasu Sakai, Yohei Shirakami, Masahito Shimizu, Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Hiroyasu Sakai, Yohei Shirakami, Masahito Shimizu, Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shirakami
authors.affiliation: Hiroyasu Sakai, Yohei Shirakami, Masahito Shimizu, Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000627:therapeutic use; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000517:prevention & control*; D002392:Catechin / Q000627:therapeutic use; D018890:Chemoprevention; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D019587:Dietary Supplements; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications; D009765:Obesity / Q000150:complications*; D013662:Tea; D014212:Tretinoin / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000597:Amino Acids, Branched-Chain; D013662:Tea; D014212:Tretinoin; C034534:3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid; D002392:Catechin
keywords: Acyclic retinoid; Branched-chain amino acids; Green tea catechins; Hepatocellular carcinoma; Obesity