Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy
Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy
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DOI：
10.1073/pnas.93.25.14795
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发表时间：
1996-12-10
影响因子：
11.1
通讯作者：
Unger, RH
中科院分区：
文献类型：
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作者：
Chen, GX;Koyama, K;Unger, RH
通过注入含有大鼠瘦素cDNA （AdCMV-leptin）的重组腺病毒，诱导正常Wistar大鼠持续高瘦素血症8 ng/ml，持续28天。高瘦素血症大鼠的食物摄入量减少了30-50%，在实验期间只增加了22克，而接受生理盐水或含有β -半乳糖苷酶基因（adcmv - β Gal）的重组病毒输注的对照动物则增加了115-132克。高瘦素血症大鼠的体脂缺失，而与高瘦素血症大鼠配对喂养的对照大鼠保留了大约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明显低于配对喂养的对照组，而脂肪酸和葡萄糖水平在两组中相似，表明高瘦素血症大鼠的胰岛素敏感性增强。因此，尽管高瘦素血症和配对喂养的动物的食物摄入量和体重增加相当，但只有前一组可识别的脂肪组织被完全消融，这增加了瘦素特异性脂肪萎缩活性的可能性。
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 approximate to 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.