Low Carbohydrate Diets: Feeding and Endocrine Signaling

描述（由申请人提供）：低碳水化合物节食计划越来越受欢迎。来自随机临床研究的最新数据表明，与低脂饮食相比，低碳水化合物饮食在6个月时间点具有增加的功效。尽管低碳水化合物饮食的流行和有效性，但对它们影响食物摄入和体重的机制知之甚少。有人认为，从碳水化合物到脂质代谢的转变导致更大的能量利用，但临床研究的数据表明，减少食物摄入量是体重减轻增加的原因。我们已经进行了动物研究，开始评估低碳水化合物饮食如何影响食物摄入和体重。我们的初步数据表明，维持在低碳水化合物-高脂肪饮食的大鼠消耗较少的食物，体重增加较少比普通的高碳水化合物-高脂肪饮食的大鼠。低碳水化合物饮食大鼠也具有增加的对黑皮质素激动剂的促食欲作用的敏感性和降低的对黑皮质素拮抗剂的促食欲作用的敏感性。此外，低碳水化合物饮食的大鼠没有显示出对食物剥夺的反弹性摄食过多，并且下丘脑基因表达对禁食的反应模式以与缺乏代偿性摄食反应一致的方式改变。这些数据表明，低碳水化合物饮食能够在不引起“饥饿”的情况下减轻体重，这是潜在的机制。所提出的实验将通过以下方式提供对消耗低碳水化合物饮食的后果的更完整的表征：1）将发现推广到与遵循阿特金斯型饮食的个体所消耗的饮食组成类似的饮食组成，2）评估对黑皮质素的反应是特异性的还是普遍适用于其他促食欲和促食欲刺激，以及评估饮食组成如何不同地改变下丘脑对伴随节食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.