通过aP2的向突变,将肥胖与胰岛素抵抗脱,aP2是脂肪细胞脂肪酸结合蛋白质
G S Hotamisligil1, R S Johnson, R J Distel
1Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. CA 92093, USA.
Science (New York, N.Y.)
|November 22, 1996
概括
缺乏脂肪细胞脂肪酸结合蛋白 (aP2) 的小鼠尽管肥胖,但仍然保持健康,这表明aP2是将肥胖与胰岛素抵抗和糖尿病联系起来的关键.
科学领域:
- 生物化学 生物化学
- 代谢疾病 代谢疾病
- 分子生物学分子生物学
背景情况:
- 脂肪酸结合蛋白 (FABPs) 是一种结合脂肪酸的小细胞质蛋白.
- FABP表现出特定于组织的表达模式.
- 脂肪细胞FABP (aP2) 在脂肪酸代谢中起作用.
研究的目的:
- 研究aP2在与肥胖相关的胰岛素耐药性发展中的作用.
- 为了确定aP2缺乏是否影响对高脂肪饮食的代谢反应.
- 探索aP2,脂肪酸代谢和肥胖中的炎症标志物之间的联系.
主要方法:
- 在aP2基因 (aP2-/-) 中具有零突变的小鼠的生成和表征.
- 给野生型和aP2-/-小鼠提供高脂肪饮食以诱导肥胖.
- 评估代谢参数,包括胰岛素敏感性和葡萄糖耐受性.
- 测量脂肪组织基因表达,包括瘤亡因子-α (TNF-α).
主要成果:
- 缺乏aP2的小鼠在发育和代谢上正常.
- 肥胖的aP2-/-小鼠没有发展胰岛素抵抗或糖尿病,与肥胖的野生类型对照不同.
- 肥胖的aP2-/-小鼠未能在脂肪组织中表达TNF-alpha,这是与胰岛素抵抗相关的分子.
结论:
- aP2是连接肥胖与胰岛素抵抗的途径中的关键调解者.
- aP2可能会将脂肪酸代谢与脂肪组织中TNF-alpha的表达联系起来.
- 准aP2可能为预防与肥胖相关的代谢功能障碍提供一种新的治疗策略.
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