Leptin and insulin down-regulate angiopoietin-like protein 3, a plasma triglyceride-increasing factor
Leptin and insulin down-regulate angiopoietin-like protein 3, a plasma triglyceride-increasing factor
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DOI：
10.1016/j.bbrc.2004.08.024
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发表时间：
2004-09-24
影响因子：
3.1
通讯作者：
Shimomura, L
中科院分区：
文献类型：
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作者：
Shimamura, M;Matsuda, M;Shimomura, L
血管生成素样蛋白3（angiopoietin-like protein 3，ANGPTL 3）是一种肝脏特异性分泌因子，可通过激活脂肪分解，抑制脂蛋白脂酶和游离脂肪酸（free fatty acid，FFA），增加血浆甘油三酯（glyceride，TG）。目前的研究检查了瘦素和胰岛素对Angptl 3的调节，瘦素和胰岛素都是代谢综合征的关键参与者。相对于对照，在瘦素抗性C57 BL/6 J（db/db）和瘦素缺陷C57 BL/6 J（ob/ob）小鼠中，Angptl 3表达和血浆ANGPTL 3水平增加。瘦素补充剂降低C57 BL/6 J（ob/ob）小鼠中的Angptl 3基因表达和血浆ANGPTL 3。Angptl 3的变化与血浆TG和FFA水平的变化相关。瘦素处理直接抑制肝细胞中的Angptl 3基因表达。在胰岛素缺乏的链脲佐菌素治疗的小鼠中，Angptl 3基因表达和血浆蛋白水平也增加。胰岛素处理肝细胞降低Angptl 3基因表达和蛋白分泌。我们的结果表明，瘦素或胰岛素抵抗导致的ANGPTL 3升高归因于肥胖患者血浆TG和FFA浓度的升高。(C)2004年由Elsevier Inc.出版
We reported previously that angiopoietin-like protein3 (ANGPTL3), a liver-specific secretory factor, increased plasma triglyceride (TG) via inhibition of lipoprotein lipase and free fatty acid (FFA) by activating adipose-lipolysis. The current study examined the regulation of Angptl3 by leptin and insulin, both of which are key players in the metabolic syndrome. Angptl3 expression and plasma ANGPTL3 levels were increased in leptin-resistant C57BL/6J(db/db) and -deficient C57BL/6J(ob/ob) mice, relative to the control. Leptin supplements decreased Angptl3 gene expression and plasma ANGPTL3 in C57BL/6J(ob/ob) mice. The changes of Angptl3 were associated with alterations of plasma TG and FFA levels. Leptin treatment directly suppressed Angptl3 gene expression in hepatocytes. Angptl3 gene expression and plasma protein levels were also increased in insulin-deficient streptozotocin-treated mice. Insulin treatment of hepatocytes decreased Angptl3 gene expression and protein secretion. Our results suggest that elevated ANGPTL3 by leptin- or insulin-resistance is attributed to increased plasma TG and FFA concentrations in obesity. (C) 2004 Published by Elsevier Inc.