瘦素在肝脏中的生理功能及其在肝脏疾病中的作用

Physiological function of leptin in liver and its pathological role in liver diseases

瘦素是由肥胖基因(obese gene,ob)编码,体内瘦素主要由脂肪组织分泌,通过结合瘦素受体调节中枢及外周组织多种重要生理功能。正常肝组织不表达瘦素,但有瘦素受体的表达,通过与肝细胞瘦素受体结合,参与调节葡萄糖的产生、转运、代谢,脂肪的分解合成及胰岛素信号的调控。近年研究发现,在多种肝脏疾病状态下,血浆及肝组织局部瘦素或瘦素受体的表达发生改变,通过干扰胰岛素信号功能、激活肝星状细胞(hepatic stellate cell,HSC)、介导肝Kupffer细胞的激活,进而诱导多种促炎、促细胞增殖及纤维化的相关基因表达,加剧了炎症细胞的浸润、细胞外基质堆积,在肝脏炎性反应、肝纤维化以及肝细胞癌发生发展中发挥作用。本文对瘦素在肝脏中的作用及其与肝病的关系进行综述。

Leptin,the protein product of the obese gene（ob）,is synthesized mainly in adipocytes and exerts important physiological functions both on central nervous system as well as peripheral tissues.Normal liver tissue does not express leptin,but does express leptin receptors.By binding to its receptor,leptin regulates multiple liver functions ranging from glucose production and transportation,lipid metabolism and insulin action.Elevated expression of leptin and its receptors have been recently detected in the patients with various liver diseases,and involved in activation of hepatic stellate cells and Kupffer cells,promoting proinflammatory genes expression,extra-cellular matrix accumulation and cell proliferation,which results in steatohepatitis,liver fibrosis and cirrhosis,and hepatocellular carcinoma.This review summarizes the recent studies on the functional studies of leptin under both physiologic and pathologic conditions.