The roles of leptin and adiponectin: A novel paradigm in adipocytokine regulation of liver fibrosis and stellate cell biology
The roles of leptin and adiponectin: A novel paradigm in adipocytokine regulation of liver fibrosis and stellate cell biology
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DOI：
10.1016/s0002-9440(10)62476-5
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发表时间：
2005-06-01
影响因子：
6
通讯作者：
Anania, FA
中科院分区：
文献类型：
--
作者：
Ding, XK;Saxena, NK;Anania, FA
虽然瘦素是促进肝纤维化的关键脂肪因子，但脂联素可能预防肝损伤。为了确定这些脂肪因子在肝纤维化中的作用，并了解它们在体内的表达，对fa/fa大鼠及其瘦的同窝仔进行胆管结扎（BDL）。胶原蛋白和α-平滑肌肌动蛋白（α-SMA）的组织形态学测定显示，瘦大鼠（而非fa/fa同窝仔）具有显著的纤维化和丰富的肝星状细胞（HSC）活化。瘦BDL大鼠肝静脉中瘦素浓度显著高于瘦假手术、fa/fa BDL或fa/fa假手术大鼠。免疫组化法观察瘦素和α-SMA在活化HSC中的共定位。实时逆转录-聚合酶链反应和蛋白质印迹分析证实了瘦素和α-SMA在活化的HSC中的存在，而不是静止的HSC，而只有静止的HSC合成脂联素mRNA和蛋白。活化HSC中脂联素过表达减少增殖，增加凋亡，并减少α-SMA和增殖细胞核抗原的表达。脂联素受体（AdipoR 1和AdipoR 2）在活化和静止的HSC中均被检测到，但只有活化的HSC在用球状或全长脂联素处理后才产生显著的凋亡。脂联素可逆转HSC活化，维持HSC静止，或在肝纤维化中具有重要的治疗意义。
Although leptin is a key adipokine promoting liver fibrosis, adiponectin may prevent liver injury. To determine the role of these adipokines in liver fibrosis and to understand their expression in vivo, fa/fa rats and their lean littermates were subjected to bile duct ligation (BDL). Histomorphometry for collagen and a-smooth muscle actin (alpha-SMA) revealed that lean rats, but not fa/fa littermates, had significant fibrosis with abundant hepatic stellate cell (HSC) activation. The lean-BDL rats had significantly higher leptin concentrations in the hepatic vein than lean sham-operated,fa/fa BDL, or fa/fa sham-operated rats. Co-localization of leptin and alpha-SMA in activated HSCs was observed by immunohistochemistry. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis confirmed the presence of leptin and alpha-SMA in activated, but not quiescent, HSCs, whereas only quiescent HSCs synthesized adiponectin mRNA and protein. Adiponectin overexpression in activated HSCs reduced proliferation, augmented apoptosis, and reduced expression of alpha-SMA and proliferating cell nuclear antigen. Adiponectin receptors (AdipoR1 and AdipoR2) were detected in both activated and quiescent HSCs, but only activated HSCs produced significant apoptosis after treatment with either globular or full-length adiponectin. Adiponectin may act to reverse HSC activation, maintain HSC quiescence, or significantly, may have important therapeutic implications in liver fibrosis.