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近日，来自美国俄勒冈州立大学和佛罗里达大学的研究人员发现通过基因疗法将leptin直接导入脑中能够帮助肥胖大鼠减轻体重，同时不会造成显著的骨流失。
通过改变饮食快速减肥会导致骨流失情况的发生，而骨密度降低又会进一步导致老年人发生骨折的风险增加，因此利用这种方法减肥给人们生活质量带来的积极影响会大打折扣。
研究人员表示，"悠悠球"瘦身会造成减肥人群的体重出现波动，出现体重减少和增加的重复循环，而在体重减少的过程中造成的骨流失并不会随着体重增加得到恢复，因此骨流失是减肥过程中一个非常令人担心的问题。
Leptin对于正常的骨骼生长和维持以及调节机体脂肪含量方面具有重要作用，它能够告诉我们的脑部我们的身体拥有多少脂肪以及脂肪贮备是否充足，但一些肥胖个体会出现leptin抵抗的情况，导致他们的脑部不能接收机体传达的准确信息。
在这项研究中，研究人员为了探究leptin在调节体重和骨密度方面的作用，以大鼠为研究对象，通过基因疗法直接将表达leptin的腺相关病毒注入大鼠的下丘脑区域，通过注射的方式可以绕过血脑屏障将病毒直接送达脑部，减少了损失。
在导入leptin之后，研究人员观察到大鼠的体重下降了20%，同时没有出现骨流失的情况，并且接受治疗的大鼠也能够维持体重减轻的表型。研究人员还发现促进肥胖相关代谢疾病产生的腹部"坏"脂肪也大量减少。
虽然脑部注射leptin作用显著，但研究人员仍然表示这种方法是否存在副作用目前仍不清楚，还需要更多研究对该方法的安全性进行进一步验证。
Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss
Russell T Turner1,2, Michael Dube3, Adam J Branscum4, Carmen P Wong1, Dawn A Olson1, Xiaoying Zhong1, Mercedes F Kweh5, Iske V Larkin6, Thomas J Wronski5, Clifford J Rosen7, Satya P Kalra3 and Urszula T Iwaniec
Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin, n=7) or a control vector encoding green fluorescent protein (rAAV-GFP, n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (?4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (?80%), serum leptin (?77%), and serum IGF1 (?34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.