Christian Doppler Research Laboratory for Gut Inflammation, Innsbruck Medical University, Innsbruck, Austria.
Curr Med Chem. 2012;19(32):5467-73. doi: 10.2174/092986712803833254.
The adipose tissue has recently emerged as an important endocrine organ releasing numerous mediators including adipocytokines, classical cytokines and others. Adiponectin, one of the major products of adipocytes, is a prototypic anti-diabetic adipocytokine, the actions of which are mainly exerted by the activation of AMP-activated kinase and peroxisome proliferator-activated receptor alpha. This adipocytokine is one of the most abundant circulating (adipo)cytokines in health. Non-alcoholic fatty liver disease (NAFLD), the major reason for abnormal liver functions in the western world, is commonly associated with obesity, insulin resistance and decreased adiponectin serum levels. Adiponectin has many anti-inflammatory activities and suppresses tumour necrosis factor-alpha (TNFα), a cytokine of key importance in NAFLD. The anti-inflammatory effects of adiponectin are also exerted by induction of the anti-inflammatory cytokines interleukin-10 (IL-10) or IL-1 receptor antagonist and up-regulation of heme-oxygenase-1. Whereas the liver probably is not a relevant source of circulating adiponectin, it is a major target organ for many adiponectin effects. Adiponectin is able to regulate steatosis, insulin resistance, inflammation and fibrosis. NAFLD is also associated with decreased liver expression of the two adiponectin receptors (AdipoR1 and 2) thereby contributing to a state of hepatic adiponectin resistance. In contrast, most other liver diseases especially in advanced disease states exhibit increased adiponectin serum levels with highest levels observed in cirrhosis. Targeting adiponectin could evolve as a major treatment concept especially for fatty liver diseases in the future.
脂肪组织最近已成为一种重要的内分泌器官，可释放多种介质，包括脂肪细胞因子、经典细胞因子等。脂联素是脂肪细胞的主要产物之一，是一种典型的抗糖尿病脂肪细胞因子，其作用主要通过激活 AMP 激活的蛋白激酶和过氧化物酶体增殖物激活受体α来发挥。这种脂肪细胞因子是健康人群中循环（脂肪）细胞因子中最丰富的一种。非酒精性脂肪性肝病（NAFLD）是西方国家肝功能异常的主要原因，通常与肥胖、胰岛素抵抗和脂联素血清水平降低有关。脂联素有许多抗炎作用，可抑制肿瘤坏死因子-α（TNFα），TNFα 是 NAFLD 中的一种关键细胞因子。脂联素的抗炎作用还通过诱导抗炎细胞因子白细胞介素-10（IL-10）或白细胞介素-1 受体拮抗剂和血红素加氧酶-1 的上调来发挥。虽然肝脏可能不是循环脂联素的相关来源，但它是许多脂联素作用的主要靶器官。脂联素能够调节脂肪变性、胰岛素抵抗、炎症和纤维化。NAFLD 还与两种脂联素受体（AdipoR1 和 2）在肝脏中的表达降低有关，从而导致肝脏对脂联素的抵抗状态。相比之下，大多数其他肝病，尤其是在晚期疾病状态下，脂联素血清水平升高，肝硬化时达到最高水平。靶向脂联素可能成为未来治疗脂肪性肝病的主要治疗概念。
