Obesity, inflammation, and liver cancer

Abstract

Obesity has become a universal and major public health problem with increasing prevalence in both adults and children in the 21st century, even in developing countries. Extensive epidemiological studies reveal a strong link between obesity and development and progression of various types of cancers. The connection between obesity and liver cancer is particularly strong and obesity often results in liver diseases such as non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH). NASH is characterized by fatty liver inflammation and is believed to cause fibrosis and cirrhosis. The latter is a known liver cancer risk factor. In fact due to its much higher prevalence obesity may be a more substantial contributor to overall hepatocellular carcinoma burden than infection with hepatitis viruses. Here we review and discuss recent advances in elucidation of cellular and molecular alterations and signaling pathways associated with obesity and liver inflammation and their contribution to hepatocarcinogenesis.

Figure 1

Three putative mechanisms for obesity-induced and obesity-promoted hepatocarcinogenesis. ROS, reactive oxygen species; RNS, reactive nitrogen species

Figure 2

Adipokines, cytokines and hepatocarcinogenesis. Excessive free fatty acids (FFAs) can activate various immune cells and cause hepatocytes cell death. Moreover, cell debris, pro-inflammatory cytokines and adipokines can further enhance TNF and IL-6 secretion from Kupffer cells, leading to activation of downstream signaling molecules, such as STAT3 in hepatocytes which contribute to hepatocarcinogenesis.