Udomsinprasert Wanvisa, Honsawek Sittisak, Poovorawan Yong
Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand.
World J Hepatol. 2018 Oct 27;10(10):708-718. doi: 10.4254/wjh.v10.i10.708.
Adiponectin is known to play primary roles in the regulation of systemic glucose homeostasis and lipid metabolism. Interestingly, emerging evidence indicates beneficial effects of adiponectin on liver fibrosis; however, the exact mechanisms of this action remain unclear. Herein, we aimed to summarize the recent findings regarding the role of adiponectin in liver fibrogenesis and update the current comprehensive knowledge regarding usefulness of adiponectin-based treatments in liver fibrosis. Adiponectin has been demonstrated to have an anti-fibrotic action in the liver by blocking the activation of hepatic stellate cell-mediated adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptor-alpha pathways, which in turn diminish the expression of pro-fibrotic genes. In addition, hyperadiponectinemia was noted in patients with various chronic liver diseases (CLDs)-related liver fibrosis. An increase in circulating adiponectin levels was also found to be associated with the development of liver fibrosis, indicating a role of adiponectin as a non-invasive biomarker for predicting the progression of liver fibrosis. It is therefore reasonable to speculate that adiponectin may be developed as a new therapeutic candidate for the treatment of liver fibrosis. Nonetheless, future observations are still necessary to fully elucidate the extent of the effects of adiponectin on liver fibrotic outcomes, in order to modify adiponectin as an anti-fibrotic therapy that would speed up fibrosis reversal in patients with CLD.
已知脂联素在调节全身葡萄糖稳态和脂质代谢中起主要作用。有趣的是,新出现的证据表明脂联素对肝纤维化有有益作用;然而,这种作用的确切机制仍不清楚。在此,我们旨在总结关于脂联素在肝纤维化发生中作用的最新发现,并更新关于基于脂联素的治疗在肝纤维化中有用性的当前综合知识。脂联素已被证明通过阻断肝星状细胞介导的腺苷单磷酸激活的蛋白激酶和过氧化物酶体增殖物激活受体-α途径的激活而在肝脏中具有抗纤维化作用,这反过来又减少了促纤维化基因的表达。此外,在各种慢性肝病(CLD)相关肝纤维化患者中发现了高脂联素血症。循环脂联素水平的升高也被发现与肝纤维化的发展有关,表明脂联素作为预测肝纤维化进展的非侵入性生物标志物的作用。因此,合理推测脂联素可能被开发为治疗肝纤维化的新候选疗法。尽管如此,仍需要未来的观察来充分阐明脂联素对肝纤维化结局的影响程度,以便将脂联素作为一种抗纤维化疗法进行改进,从而加速CLD患者的纤维化逆转。