Centre for Translational Neuroscience, School of Health Sciences, University of Wollongong, Northfield Avenue, NSW 2522, Australia.
Behav Brain Res. 2009 Dec 14;205(1):50-6. doi: 10.1016/j.bbr.2009.07.003. Epub 2009 Jul 16.
Weight regain after weight loss is a major hurdle for combating obesity. The aim of this study is to examine orexigenic and anorectic neuropeptides of the hypothalamic arcuate nucleus (Arc) in response to weight loss after chronic energy intake restriction. Thirty mice were fed with a high-fat diet for 8 weeks and then classified as diet-induced obese (DIO; n=10) or diet-resistant (DR; n=10) mice according to the highest and lowest body weight gainers. Five mice from DIO and DR groups were placed on an energy restricted diet or continued on their high-fat diet ad libitum for 6 weeks. An additional five mice were on a LF diet throughout the course of this study as controls. Results showed that a six-week energy restricted diet completely reversed the increased body weight, fat mass and leptin in the DIO mice to the levels of the LF and DR mice. Arc neuropeptide Y (NPY) and agouti-related protein (AgRP) mRNA expression in DIO mice after obesity reversal were significantly higher than DIO mice without obesity reversal (17%, 47%, both p<0.05), while the Arc pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA showed no difference. Both NPY and AgRP expression in DIO mice were negatively correlated with plasma leptin (R=-0.78, p<0.05; R=-0.72, p<0.05). In conclusion, while chronic energy restriction will lead to weight loss, it can up-regulate hypothalamic orexigenic peptides, which may be an important contributing factor to weight regain after a weight loss program from an energy restricted diet.
体重减轻后体重的反弹是对抗肥胖的一个主要障碍。本研究旨在研究下丘脑弓状核（Arc）的食欲肽和厌食神经肽对慢性能量摄入限制后体重减轻的反应。30 只小鼠喂食高脂肪饮食 8 周，然后根据体重增加最高和最低的小鼠分为饮食诱导肥胖（DIO；n=10）或饮食抵抗（DR；n=10）小鼠。DIO 和 DR 组的 5 只小鼠被置于能量限制饮食或继续自由喂食高脂肪饮食 6 周。另外 5 只小鼠在整个研究过程中一直喂食低脂饮食作为对照。结果表明，6 周的能量限制饮食完全使 DIO 小鼠的体重、脂肪量和瘦素增加恢复到 LF 和 DR 小鼠的水平。肥胖逆转后 DIO 小鼠的 Arc 神经肽 Y（NPY）和刺鼠相关蛋白（AgRP）mRNA 表达明显高于未逆转肥胖的 DIO 小鼠（分别增加 17%和 47%，均 p<0.05），而 Arc 前阿黑皮素原（POMC）和可卡因-安非他命调节转录物（CART）mRNA 则没有差异。DIO 小鼠的 NPY 和 AgRP 表达与血浆瘦素呈负相关（R=-0.78，p<0.05；R=-0.72，p<0.05）。结论是，虽然慢性能量限制会导致体重减轻，但它会上调下丘脑食欲肽，这可能是限制饮食减肥计划后体重反弹的一个重要因素。
