Low Carbohydrate Diets: Feeding and Endocrine Signaling

描述(申请人提供)：低碳水化合物饮食计划越来越受欢迎。最近来自随机临床研究的数据表明，与低脂肪饮食相比，低碳水化合物饮食在6个月的时间点上具有更高的疗效。尽管低碳水化合物饮食很受欢迎，也很有效，但人们对它们影响食物摄入量和体重的机制知之甚少。有人提出，从碳水化合物代谢到脂肪代谢的转变会导致更高的能量利用率，但来自临床研究的数据表明，减少食物摄入量是减肥增加的原因。我们已经进行了动物研究，以开始评估低碳水化合物饮食可能会如何影响食物摄入量和体重。我们的初步数据表明，与普通高碳水化合物-高脂肪饮食的大鼠相比，低碳水化合物-高脂肪饮食的大鼠消耗的食物更少，体重增加也更少。低碳水化合物饮食的大鼠对黑素皮质素激动剂的厌食作用也有更高的敏感度，而对黑素皮质素拮抗剂的厌食作用的敏感度降低。此外，低碳水化合物饮食的大鼠不会因食物匮乏而表现出反弹的吞噬反应，而下丘脑基因表达对禁食的反应模式也会发生变化，这与缺乏代偿性摄食反应是一致的。这些数据表明，低碳水化合物饮食能够在不引起“饥饿”的情况下实现减肥的潜在机制。拟议的实验将通过以下方式提供对低碳水化合物饮食后果的更完整的描述：1)将研究结果推广到与遵循阿特金斯类型饮食的个人摄入的饮食结构相似的饮食结构；2)评估对黑素皮质素的反应是否对其他厌食和厌食刺激具有特异性或普遍性；以及3)评估饮食结构如何以不同的方式改变下丘脑对伴随节食而来的慢性食物限制状态的反应。

DESCRIPTION (provided by applicant): Low carbohydrate dieting plans are increasingly popular. Recent data from randomized clinical studies have shown that low carbohydrate diets have increased efficacy at 6 month time points as compared to low-fat diets. Despite the popularity and efficacy of low carbohydrate diets, little is known about the mechanisms through which they affect food intake and body weight. It has been suggested that transition from a carbohydrate to a lipid metabolism results in greater energy utilization but data from clinical studies suggest that reduced food intake accounts for the increased weight loss. We have conducted animal studies to begin to assess how low carbohydrate diets may affect food intake and body weight. Our preliminary data demonstrate that rats maintained on a low carbohydrate-high fat diet consume less food and gain less weight than rats on an ordinary high carbohydrate-high fat diet. Low carbohydrate diet rats also have increased sensitivity to the anorexigenic effects of a melanocortin agonist and decreased sensitivity to the orexigenic effects of a melanocortin antagonist. Furthermore, rats on a low carbohydrate diet do not show a rebound hyperphagia in response to food deprivation and patterns of hypothalamic gene expression in response to fasting are altered in a manner consistent with the lack of a compensatory feeding response. These data suggest potential mechanisms underlying the ability of low carbohydrate diets to produce weight loss without inducing "hunger". The proposed experiments will provide a more complete characterization of the consequences of consuming a low carbohydrate diet by 1) generalizing the findings to a diet composition similar to that consumed by individuals following Atkins-type diets, 2) assessing whether the response to melanocortins is specific or generalizes to other anorexigenic and orexigenic stimuli and 3) assessing how diet composition may differentially alter hypothalamic responses to the state of chronic food restriction that accompanies dieting.