Adipocytokines and Hepatocellular Carcinoma

Abstract

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.

Plasma Levels of Adiponectin and Primary Liver Cancer Risk in Middle-Aged Japanese Adults with Hepatitis Virus Infection: A Nested Case–Control Study

“…Earlier experimental studies suggested that adiponectin played a protective role in carcinogenesis via insulin sensitization, antiproliferation, anti-inflammation, and angiogenesis regulation (10), and data supported epidemiologic evidence that adiponectin levels were inversely associated with the risk of obesityrelated malignancies, such as breast, colorectal, endometrium, and prostate cancers (10). These results also suggested that elevated levels of adiponectin would be associated with a reduced risk of primary liver cancer linked with obesity, and that hyperadiponectinemia might suppress liver tumorigenesis (11). Indeed, experimental studies indicated that adiponectin treatment increased apoptosis of hepatocelluar carcinoma, the most common form of primary liver cancer, and inhibited its proliferation (12,13).…”

“…Indeed, experimental studies indicated that adiponectin treatment increased apoptosis of hepatocelluar carcinoma, the most common form of primary liver cancer, and inhibited its proliferation (12,13). However, it has been pointed out that hyperadiponectinemia reflects the progression of liver disease leading to the development of liver cancer, as the liver is the main organ of adiponectin metabolism (9,11). A recent hospital-based cohort study showed that high serum levels of adiponectin were positively associated with the development of hepatocelluar carcinoma in patients with chronic hepatitis C (14).…”

Annexin A6 protein is downregulated in human hepatocellular carcinoma

“…Hypoadiponectinemia in NAFLD contributes to liver steatosis and inflammation. This adipokine is further supposed to protect from HCC [1,22].…”

Secretion of One Adipokine Nampt/Visfatin Suppresses the Inflammatory Stress‐Induced NF‐κB Activity and Affects Nampt‐Dependent Cell Viability in Huh‐7 Cells

“…Adipokines such as adiponectin as well as leptin have been demonstrated in the obesity-associated disorders, nonalcohol fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) [30]. Recent study has demonstrated that adiponectin rather than leptin or visfatin (eNampt) is associated with HBV or metabolic induced HCC [31].…”