Short-days induce weight loss in Siberian hamsters despite overexpression of the agouti-related peptide gene.
Short-days induce weight loss in Siberian hamsters despite overexpression of the agouti-related peptide gene.
复制标题
尽管刺鼠相关肽基因过度表达，但短日照仍会导致西伯利亚仓鼠体重减轻。
DOI：
10.1111/j.1365-2826.2010.02001.x
复制
发表时间：
2010
影响因子：
3.2
通讯作者：
Jethwa PH
中科院分区：
文献类型：
--
作者：
Jethwa PH
许多脊椎动物表现出深刻的身体肥胖的年度周期，尽管尚不清楚这些周期是否代表了调节食物摄取和能量消耗的动态平衡控制的中央通路的不同活动，或者是否最近发现的结节部的主要作用-室管膜信号点通向新的机制。我们在西伯利亚仓鼠(Photopus Sungorus)身上进行了这方面的研究，方法是通过基因导入上调主要的食欲肽--刺鼠相关肽(AgRP)，然后确定这种增加的合成代谢驱动是否可以防止短日照诱导的冬季分解代谢状态。将编码agrp结构的重组腺相关病毒注射到季节性周期中长时间肥胖阶段的仓鼠的下丘脑中，与接受对照报告结构的仓鼠相比，在6 周内体重增加了20%，反映出摄食量显著增加，能量消耗显著减少。然而，尽管表达AgRP结构的仓鼠与对照组相比保持了更高的食物摄入量和更低的能量消耗，但所有的仓鼠在暴露于短光周期时都显示出显著的、持续的体重下降。绿色荧光蛋白报告的可视化和AgRP免疫反应性分析证实，该结构在下丘脑中广泛表达，并在21周的研究期间保持不变。总之，下丘脑AgRP的过度表达导致了严重肥胖状态，但并没有阻止季节性分解代谢反应，这表明季节性的血流变机制与维持能量代谢的动态平衡的机制是分开的。
Many vertebrates express profound annual cycles of body fattening, although it is not clear whether these represent differential activity of the central pathways known to mediate homeostatic control of food intake and energy expenditure, or whether the recent discovery of a major role for pars tuberalis‐ependymal signalling points towards novel mechanisms. We examined this in the Siberian hamster (Phodopus sungorus) by using gene transfection to up‐regulate a major orexigenic peptide, agouti‐related peptide (AgRP), and then determined whether this increased anabolic drive could prevent the short‐day induced winter catabolic state. Infusions of a recombinant adeno‐associated virus encoding an AgRP construct into the hypothalamus of hamsters in the long‐day obese phase of their seasonal cycle produced a 20% gain in body weight over 6 weeks compared to hamsters receiving a control reporter construct, reflecting a significant increase in food intake and a significant decrease in energy expenditure. However, all hamsters showed a significant, prolonged decrease in body weight when exposed to short photoperiods, despite the hamsters expressing the AgRP construct maintaining a higher food intake and lower energy expenditure relative to the control hamsters. Visualisation of the green fluorescent protein reporter and analysis of AgRP‐immunoreactivity confirmed widespread expression of the construct in the hypothalamus, which was maintained for the 21‐week duration of the study. In conclusion, the over‐expression of AgRP in the hypothalamus produced a profoundly obese state but did not block the seasonal catabolic response, suggesting a separation of rheostatic mechanisms in seasonality from those maintaining homeostasis of energy metabolism.