摘要
The risk factors for hepatocellular carcinoma (HCC) development have been established,and include chronic hepatitis B and C,heavy alcohol consumption,and aflatoxins.In fact,5%-30% of patients with HCC still lack a readily identifiable risk factor.It has been reported that the majority of "cryptogenic" HCC may be attributed to nonalcoholic fatty liver disease,the hepatic presentation of the metabolic syndrome (MS).Obesity is associated with the development of the MS.Recently,adipose tissue has been considered as an endocrine organ because of its capacity to secrete a variety of cytokines,which are collectively known as the adipokines.Leptin,the product of the obese gene,is mainly produced by adipose tissue.Since leptin was first characterized in 1994,accumulated literature has demonstrated the involvement of this adipokine in several areas of human physiology.After binding to its receptor,leptin initiates a cascade of signaling events and subsequent cellular effects.In addition to being the regulatory mediator of energy homeostasis,several in vitro studies have demonstrated the fibrogenic role of leptin in the liver.Furthermore,the deregulated expression of leptin and its receptor have been demonstrated to be associated with a variety of metabolic disorders as well as human cancers.Most importantly,direct evidence supporting the inhibitory and/or activating role of leptin in the process of carcinogenesis and progression of human HCC has been accumulating rapidly.This review aims to provide important insights into the potential mechanisms of leptin in the development of HCC.Hopefully,further investigations will shed light on a new therapeutic target in HCC.
The risk factors for hepatocellular carcinoma (HCC) development have been established,and include chronic hepatitis B and C,heavy alcohol consumption,and aflatoxins.In fact,5%-30% of patients with HCC still lack a readily identifiable risk factor.It has been reported that the majority of 'cryptogenic' HCC may be attributed to nonalcoholic fatty liver disease,the hepatic presentation of the metabolic syndrome (MS).Obesity is associated with the development of the MS.Recently,adipose tissue has been considered as an endocrine organ because of its capacity to secrete a variety of cytokines,which are collectively known as the adipokines.Leptin,the product of the obese gene,is mainly produced by adipose tissue.Since leptin was first characterized in 1994,accumulated literature has demonstrated the involvement of this adipokine in several areas of human physiology.After binding to its receptor,leptin initiates a cascade of signaling events and subsequent cellular effects.In addition to being the regulatory mediator of energy homeostasis,several in vitro studies have demonstrated the fibrogenic role of leptin in the liver.Furthermore,the deregulated expression of leptin and its receptor have been demonstrated to be associated with a variety of metabolic disorders as well as human cancers.Most importantly,direct evidence supporting the inhibitory and/or activating role of leptin in the process of carcinogenesis and progression of human HCC has been accumulating rapidly.This review aims to provide important insights into the potential mechanisms of leptin in the development of HCC.Hopefully,further investigations will shed light on a new therapeutic target in HCC.
基金
Supported by Kaohsiung Medical University Hospital Cancer Center through funding by the Department of Health,Taiwan,China
NSC Grant 95-2314-B-037-046 from the National Science Council,Taiwan,China
