腺病毒介导的瘦素基因治疗诱导正常大鼠体内脂肪消失。
Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy.
作者信息
Chen G, Koyama K, Yuan X, Lee Y, Zhou Y T, O'Doherty R, Newgard C B, Unger R H
机构信息
Gifford Laboratories for Diabetes Research, University of Texas Southwestern Medical Center, Dallas 75235, USA.
出版信息
Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14795-9. doi: 10.1073/pnas.93.25.14795.
Sustained hyperleptinemia of 8 ng/ml was induced for 28 days in normal Wistar rats by infusing a recombinant adenovirus containing the rat leptin cDNA (AdCMV-leptin). Hyperleptinemic rats exhibited a 30-50% reduction in food intake and gained only 22 g over the experimental period versus 115-132 g in control animals that received saline infusions or a recombinant virus containing the beta-galactosidase gene (AdCMV-beta Gal). Body fat was absent in hyperleptinemic rats, whereas control rats pair-fed to the hyperleptinemic rats retained approximately 50% body fat. Further, plasma triglycerides and insulin levels were significantly lower in hyperleptinemic versus pair-fed controls, while fatty acid and glucose levels were similar in the two groups, suggestive of enhanced insulin sensitivity in the hyperleptinemic animals. Thus, despite equivalent reductions in food intake and weight gain in hyperleptinemic and pair-fed animals, identifiable fat tissue was completely ablated only in the former group, raising the possibility of a specific lipoatrophic activity for leptin.
通过向正常的Wistar大鼠输注含有大鼠瘦素cDNA的重组腺病毒（AdCMV-瘦素），诱导其持续28天出现8 ng/ml的高瘦素血症。高瘦素血症大鼠的食物摄入量减少了30%-50%，在实验期间体重仅增加了22 g，而接受生理盐水输注或含有β-半乳糖苷酶基因的重组病毒（AdCMV-βGal）的对照动物体重增加了115-132 g。高瘦素血症大鼠体内没有体脂，而与高瘦素血症大鼠配对饲养的对照大鼠保留了约50%的体脂。此外，高瘦素血症大鼠的血浆甘油三酯和胰岛素水平显著低于配对饲养的对照大鼠，而两组的脂肪酸和葡萄糖水平相似，这表明高瘦素血症动物的胰岛素敏感性增强。因此，尽管高瘦素血症动物和配对饲养动物的食物摄入量和体重增加都有同等程度的减少，但只有前一组的可识别脂肪组织完全消失，这增加了瘦素具有特定脂肪萎缩活性的可能性。
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