Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.394
Peer-review started: June 2, 2015
First decision: August 31, 2015
Revised: October 14, 2015
Accepted: November 24, 2015
Article in press: November 24, 2015
Published online: January 7, 2016
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.
Core tip: Obesity and its related metabolic disorders increase the risk of hepatocellular carcinoma (HCC). In particular, the molecular abnormalities represented by insulin resistance/hyperinsulinemia, chronic inflammation, adipokine imbalance, and oxidative stress play a central role in the development of obesity-related HCC. Administration of green tea catechins, branched-chain amino acids, and acyclic retinoid has improved these metabolic abnormalities, and resulted in the inhibition of HCC development in obese and diabetic mice models. In this review, we highlight the possibility that nutraceutical and pharmaceutical approaches targeting metabolic abnormalities are a promising strategy to prevent the development of obesity-related HCC.