【转帖】节食行为会导致压力相关基因表达的长期变化

为了验证这一假说，研究者在3周的时间里将被试小鼠的日常饮食量减少了25%，直到它们的体重降低了10%~15%。这与人类在中等程度节食下达到中等程度减重目标的水平相仿。

然后，研究人员将这些小鼠置于一些比较温和的压力环境中，比如给它们施加噪音等。他们发现，节食组小鼠血液中的皮质醇含量要比对照组的高，这说明节食使得小鼠倍感压力，并需要花费更多的时间来恢复平静。

随后，研究人员让这些小鼠恢复饮食以回到初始体重，以此来模拟人类“减肥——反弹——再减肥”的典型现象。在进食了1周的实验室标准饲料后，这些小鼠又被重新置于压力环境中，以模拟人类日常生活中的起伏跌宕。

研究结果表明，节食的小鼠仍然比对照组更容易感知到压力的存在，并且它们在压力影响下，也会更倾向于进食大量高热量的食物。研究者的这一结果发表在最近出版的《神经科学》杂志上。

研究人员同时发现，就算是短期、温和的节食行为也会导致基因表达方面的长期变化。节食的小鼠体内用于刺激皮质醇释放的蛋白质水平明显偏高，这说明它们对压力更为敏感；并且给它们提供高脂肪食物后，它们体内用于食欲刺激的激素水平也较高。

“这种现象说明，诸如节食和高热量食物刺激等环境因素，可能会导致基因表达的长期变化，而这些变化将会影响小鼠的饮食习惯和应对压力的方式。”美国北卡罗来纳大学教堂山分校的心理学家Cynthia Bulik评论称，她同时也是该校“饮食紊乱症项目”的负责人。

基因表达方面的变化或许能够解释为什么许多节食减肥的行为都失败了。节食先是提高了人们对压力的敏感性，然后压力又使得人们倾向于从高脂肪、高热量的食物中寻求“慰藉”。

“节食减肥困难重重，这是因为你的大脑一直在和你作对。”Bale表示。而学会更好地应对压力或许才是成功减肥的关键，这是因为“如果没有压力，你就不会总想要暴饮暴食”。

Bale认为，设计针对压力的药物，或许能够帮助节食者保持住他们好不容易才减下来的体重。

The Journal of Neuroscience doi:10.1523/JNEUROSCI.1955-10.2010

Caloric Restriction Experience Reprograms Stress and Orexigenic Pathways and Promotes Binge Eating

Diana E. Pankevich, Sarah L. Teegarden, Andrew D. Hedin, Catherine L. Jensen, and Tracy L. Bale

Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Long-term weight management by dieting has a high failure rate. Pharmacological targets have focused on appetite reduction, although less is understood as to the potential contributions of the stress state during dieting in long-term behavioral modification. In a mouse model of moderate caloric restriction in which a 10–15% weight loss similar to human dieting is produced, we examined physiological and behavioral stress measures. After 3 weeks of restriction, mice showed significant increases in immobile time in a tail suspension test and stress-induced corticosterone levels. Increased stress was associated with brain region-specific alterations of corticotropin-releasing factor expression and promoter methylation, changes that were not normalized with refeeding. Similar outcomes were produced by high-fat diet withdrawal, an additional component of human dieting. In examination of long-term behavioral consequences, previously restricted mice showed a significant increase in binge eating of a palatable high-fat food during stress exposure. Orexigenic hormones, melanin-concentrating hormone (MCH) and orexin, were significantly elevated in response to the high-fat diet only in previously restricted mice. Furthermore, administration of the MCH receptor-1 antagonist GSK-856464 [4-(4-ethyl-5-methylsulfanyl-1,2,4-triazol-3-yl)pyridine] significantly reduced total caloric intake in these mice during high-fat access. These results reveal reprogramming of key central pathways involved in regulating stress responsivity and orexigenic drives by moderate caloric restriction experience. In humans, such changes would be expected to reduce treatment success by promoting behaviors resulting in weight regain, and suggest that management of stress during dieting may be beneficial in long-term maintenance.

看来一些人是不能节食的了。