Adipose tissue transplantation protects ob/ob mice from obesity, normalizes insulin sensitivity and restores fertility
Adipose tissue transplantation protects ob/ob mice from obesity, normalizes insulin sensitivity and restores fertility
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DOI：
10.1677/joe.1.06150
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发表时间：
2005-07-01
影响因子：
4
通讯作者：
Harrison, DE
中科院分区：
文献类型：
--
作者：
Klebanov, S;Astle, CM;Harrison, DE
脂肪组织通过分泌各种脂肪因子影响新陈代谢。脂肪代谢障碍小鼠受益于瘦素替代疗法和正常体型移植。瘦素缺陷的 Lep(ob)/Lep(ob) (ob/ob) 小鼠也可以用瘦素治疗。令人惊讶的是，目前还没有通过移植正常白色脂肪组织（WAT）成功治疗肥胖 ob/ob 小鼠的报道。如果 WAT 移植对治疗肥胖个体的胰岛素抵抗和糖尿病无效，则其在人类中的适用性可能会受到限制，因为此类异常通常与肥胖有关。在当前的研究中，我们测试了 WAT 移植是否可以预防甚至逆转 ob/ob 小鼠的异常特征。为了评估预防潜力，将正常小鼠的性腺脂肪垫皮下移植到 6 周大的 ob/ob 小鼠。尽管瘦素水平低于对照小鼠的 25%，但对多种生理表型产生了深远的影响。来自一名捐赠者的 WAT 减少了 ob/ob 小鼠的体重增加，而来自 4 或 8 名捐赠者的 WAT 则防止了肥胖。非空腹胰岛素水平和胰岛素耐量测试正常化。皮质酮升高也得到了预防。最后，4 名捐赠者的 WAT 恢复了 ob/ob 女性的生育能力。 WAT 移植的效果是持久的，体重增加被抑制至少 40 周。为了评估治疗潜力，使用了具有长期瘦素缺乏史的肥胖 13 个月大 ob/ob 小鼠。当移植 8 名捐赠者的 WAT 后，他们的体重下降了约 50%。与年轻接受者一样，移植大大降低了非空腹胰岛素，表明胰岛素敏感性正常化。因此，WAT移植对于预防和治疗都是有效的。未来，WAT 移植可能成为激素替代疗法的有效替代方案，不仅可以治疗脂肪代谢障碍，还可以治疗某些类型的肥胖症。
Adipose tissue affects metabolism by secreting various adipokines. Lipodystropic mice benefit both from leptin replacement therapy and from transplantation of normal fit. Leptin-deficient Lep(ob)/Lep(ob) (ob/ob) mice can also be treated with leptin. Surprisingly, there have been no reports of successful treatment of obese ob/ob mice by transplantation of normal white adipose tissue (WAT). If WAT transplantation is ineffective in treating insulin resistance and diabetes in obese individuals, its applicability may be limited in humans as such abnormalities are usually associated with obesity. In the current study, we tested whether WAT transplantation might prevent, and even reverse, abnormalities characteristic of ob/ob mice. To assess the preventive potential, 6-week-old ob/ob mice were transplanted, subcutaneously, with gonadal fat pads from normal mice. profound effects on multiple physiological phenotypes were achieved despite leptin levels below 25% of those in control mice. WAT from one donor reduced body weight gain, and WAT from 4 or 8 donors prevented obesity in ob/ob mice. Nonfasting insulin levels and insulin tolerance test were normalized. Corticosterone elevation was also prevented. Finally, WAT from 4 donors restored fertility in ob/ob females. The effects of WAT transplantation were long-lasting, with body weight gain suppressed for at least 40 weeks. To assess the therapeutic potential, obese 13-month-old ob/ob mice with a long history of leptin deficiency were used. Their body weight decreased by approximately 50% when transplanted with WAT from 8 donors. As in young recipients, transplantation greatly reduced nonfasting insulin, suggesting normalized insulin sensitivity. Thus, WAT transplantation was effective for both prevention and therapy. In the future, WAT transplantation may become a useful alternative to hormone replacement in treating not only lipodystropy, but also certain types of obesity.