Adipocytokines and hepatocellular carcinoma

Adipocytokines are primarily adipocyte-derived products, although certain members are also synthesized by other cell types. These adipocytokines, similarly to classical cytokines, are characterized by very pleiotropic functions affecting biological processes throughout the body. An increasing number of adipocytokines has recently been recognized, such as adiponectin, leptin, pre-B cell colony-enhancing factor/Nampt/visfatin, resistin, progranulin, and others. Adiponectin has emerged as the most abundant circulating adipocytokine, is produced almost exclusively by adipocytes, and has mainly anti-inflammatory and anti-diabetic functions. In contrast, leptin is produced by many cell types beyond adipocytes, regulates immunity and T cell functions, and acts in a more pro-inflammatory fashion. Adipocytokines play a fundamental role in adipose tissue homeostasis (i.e. health) and disease, especially in obesity-related disorders such as non-alcoholic fatty liver diseases (NAFLD) and their complications, including hepatocellular carcinoma (HCC). Lack of adiponectin as observed in NAFLD drives steatosis and inflammation in the liver, and evidence is increasing that this adipocytokine has many anti-tumor properties and might play a rather protective role in HCC. The role of leptin in NAFLD is still unclear and this adipocytokine seems to have opposite effects in HCC, acting more as a tumor promoter. Evidence is increasing that HCC tissue produces various adipocytokines, and adiponectin expression in HCC seems to be decreased whereas leptin expression is rather increased. In conclusion, adipocytokines are increasingly recognized as pleiotropic molecules involved in the pathophysiology of HCC, which might lead to therapeutic approaches targeting these mediators.