Angiopoietin-related growth factor antagonizes obesity and insulin resistance
Angiopoietin-related growth factor antagonizes obesity and insulin resistance
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DOI：
10.1038/nm1214
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发表时间：
2005-04-01
期刊：
影响因子：
82.9
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Oike, Y;Akao, M;Suda, T
血管生成素相关生长因子（AGF）是血管生成素样蛋白（Angptl）家族的成员，主要从肝脏分泌到体循环中。在这里，我们发现大多数（> 80%）的AGF缺陷小鼠在胚胎第13天左右死亡，而存活的AGF缺陷小鼠发展为明显的肥胖，骨骼肌和肝脏中的脂质积聚，以及胰岛素抵抗，伴随着相对于对照组的能量消耗减少。同时，具有AGF靶向激活的小鼠显示出由增加的能量消耗引起的消瘦和增加的胰岛素敏感性。他们也受到保护，免受高脂肪饮食诱导的肥胖，胰岛素抵抗和非脂肪组织脂肪变性。通过腺病毒转导导致血清AGF浓度增加约2.5倍的AGF肝脏过表达，导致喂食高脂饮食的小鼠体重显著减轻（P < 0.01）并增加胰岛素敏感性。这项研究确定AGF作为一种新的肝细胞衍生的循环因子，可以抵消肥胖和相关的胰岛素抵抗。
Angiopoietin-related growth factor (AGF), a member of the angiopoietin-like protein (Angptl) family, is secreted predominantly from the liver into the systemic circulation. Here, we show that most (> 80%) of the AGF-deficient mice die at about embryonic day 13, whereas the surviving AGF-deficient mice develop marked obesity, lipid accumulation in skeletal muscle and liver, and insulin resistance accompanied by reduced energy expenditure relative to controls. In parallel, mice with targeted activation of AGF show leanness and increased insulin sensitivity resulting from increased energy expenditure. They are also protected from high-fat diet - induced obesity, insulin resistance and nonadipose tissue steatosis. Hepatic overexpression of AGF by adenoviral transduction, which leads to an approximately 2.5-fold increase in serum AGF concentrations, results in a significant ( P < 0.01) body weight loss and increases insulin sensitivity in mice fed a high-fat diet. This study establishes AGF as a new hepatocyte-derived circulating factor that counteracts obesity and related insulin resistance.