Sirohi S, Van Cleef A, Davis J F
Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA.
Int J Obes (Lond). 2017 Mar;41(3):412-419. doi: 10.1038/ijo.2016.235. Epub 2016 Dec 27.
Selection of a healthy diet is the cornerstone for treating obesity and metabolic disease. Unfortunately, the majority of diets fail leading to weight regain and in some cases, pathological feeding behavior. We hypothesize that alternating bouts of caloric overconsumption and caloric restriction, behavioral manifestations of dieting induce neuroendocrine, behavioral and genetic changes that promote future bouts of palatable food intake.
To test this hypothesis, we subjected male Long-Evans rats to a high-fat diet (HFD) feeding paradigm that induced a pattern of caloric overconsumption and caloric restriction. Under these conditions we measured operant responding for sucrose, pre-meal ghrelin secretion, the effects of peripheral ghrelin blockade on patterned feeding, HFD intake in an aversive environment and mRNA expression of the ghrelin receptor, orexin, orexin-1 and 2 receptors, and FTO in the medial prefrontal cortex, lateral hypothalamus and ventral tegmental area.
Rats subjected to this feeding regimen displayed increased ghrelin levels prior to HFD exposure and blockade of this response attenuated patterned feeding behavior. In addition, patterned feeding promoted enhanced motivation for sucrose, diminished extinction of this response and increased HFD intake in an aversive environment. The neuroendocrine and behavioral changes correlated with increased hypothalamic expression of the ghrelin receptor and FTO.
Collectively, these data indicate that patterns of feeding that include caloric overconsumption and caloric restriction induce neuroendocrine and neurobiological changes that signify an enhanced drive for palatable food.
选择健康饮食是治疗肥胖和代谢性疾病的基石。不幸的是,大多数节食方法都失败了,导致体重反弹,在某些情况下还会出现病理性进食行为。我们假设,热量过度摄入和热量限制的交替发作,即节食的行为表现,会诱发神经内分泌、行为和基因变化,从而促进未来对美味食物的摄入。
为了验证这一假设,我们让雄性长爪沙鼠接受高脂饮食(HFD)喂养模式,这种模式会导致热量过度摄入和热量限制。在这些条件下,我们测量了对蔗糖的操作性反应、餐前胃饥饿素分泌、外周胃饥饿素阻断对模式化进食的影响、在厌恶环境中对高脂饮食的摄入量,以及内侧前额叶皮质、外侧下丘脑和腹侧被盖区中胃饥饿素受体、食欲素、食欲素-1和-2受体以及FTO的mRNA表达。
接受这种喂养方案的大鼠在接触高脂饮食前胃饥饿素水平升高,阻断这种反应可减弱模式化进食行为。此外,模式化进食增强了对蔗糖的动机,减少了这种反应的消退,并增加了在厌恶环境中对高脂饮食的摄入量。神经内分泌和行为变化与下丘脑胃饥饿素受体和FTO表达增加相关。
总体而言,这些数据表明,包括热量过度摄入和热量限制的进食模式会诱发神经内分泌和神经生物学变化,这表明对美味食物的驱动力增强。