Kamada Yoshihiro, Takehara Tetsuo, Hayashi Norio
Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka 565-0871, Japan.
J Gastroenterol. 2008;43(11):811-22. doi: 10.1007/s00535-008-2213-6. Epub 2008 Nov 18.
Adipose tissue is a massive source of bioactive substances known as adipocytokines, including tumor necrosis factor (TNF)-alpha, resistin, leptin, and adiponectin. Recent advances in medical research view obesity as a chronic low-grade inflammatory state. Hypertrophied adipocytes in obesity release chemokines that induce macrophage accumulation in adipose tissue. Accumulated macrophages in obese adipose tissue produce proinflammatory cytokines and nitric oxide, and these inflammatory changes induce adipocytokine dysregulation. The latter is characterized by a decrease in insulinsensitizing and anti-inflammatory adipocytokines, and an increase in proinflammatory adipocytokines. Adipocytokine dysregulation induces obesity-related metabolic disorders, the so-called metabolic syndrome. Metabolic syndrome is a cluster of metabolic abnormalities, including diabetes mellitus, hypertension, hyperlipidemia, and nonalcoholic steatohepatitis (NASH). Recent studies have revealed that obesity is an independent risk factor for chronic liver diseases, such as NASH, alcoholic liver disease, chronic hepatitis C, and hepatocellular carcinoma. A common mechanism underlying these hepatic clinical states is thought to be adipocytokine dysregulation. In this review, we discuss the association of adipocytokines, especially leptin, adiponectin, TNF-alpha, and resistin, with liver diseases.
脂肪组织是生物活性物质(即脂肪细胞因子)的重要来源,包括肿瘤坏死因子(TNF)-α、抵抗素、瘦素和脂联素。医学研究的最新进展将肥胖视为一种慢性低度炎症状态。肥胖状态下肥大的脂肪细胞会释放趋化因子,促使巨噬细胞在脂肪组织中聚集。肥胖脂肪组织中聚集的巨噬细胞会产生促炎细胞因子和一氧化氮,这些炎症变化会导致脂肪细胞因子失调。后者的特征是胰岛素敏感性和抗炎性脂肪细胞因子减少,促炎性脂肪细胞因子增加。脂肪细胞因子失调会引发肥胖相关的代谢紊乱,即所谓的代谢综合征。代谢综合征是一系列代谢异常,包括糖尿病、高血压、高脂血症和非酒精性脂肪性肝炎(NASH)。最近的研究表明,肥胖是慢性肝病(如NASH、酒精性肝病、慢性丙型肝炎和肝细胞癌)的独立危险因素。这些肝脏临床状态的一个共同潜在机制被认为是脂肪细胞因子失调。在这篇综述中,我们讨论脂肪细胞因子,尤其是瘦素、脂联素、TNF-α和抵抗素与肝脏疾病的关联。