Mobbs Charles V, Isoda Fumiko, Makimura Hideo, Mastaitis Jason, Mizuno Tooru, Shu I-Wei, Yen Kelvin, Yang Xue-jun
Fishberg Center for Neuroscience Neurobiology of Aging Laboratories, P.O. Box 1639 and Department of Geriatrics, Mt. Sinai School of Medicine, 1 Gustave Levy Pl., New York, NY 10029-6574, United States.
Physiol Behav. 2005 May 19;85(1):3-23. doi: 10.1016/j.physbeh.2005.04.005.
Since nutrition-sensitive feedback signals normally act to maintain relatively stable levels of both available and stored nutritional resources, failure in one or more of these feedback signals could plausibly lead to obese phenotypes. The glucostatic hypothesis in its original form posited that glucose serves as a physiological satiety factor (in the sense that post-prandial increases in plasma glucose cause meal termination), but in this form the hypothesis has been difficult to prove, and, especially since the discovery of leptin, the glucostatic hypothesis has largely been abandoned. Nevertheless, reduction of plasma glucose levels or glucose signaling produces a profile of neuroendocrine responses similar to those produced by leptin deficiency. Since leptin is not a physiological satiety factor (because it does not increase before meal termination), yet leptin deficiency causes obesity, we suggest that the glucostatic hypothesis be re-formulated without reference to satiety (i.e., short-term effects on food intake). Instead we argue that like leptin signaling, glucose signaling regulates long-term energy balance, in part by regulating metabolic rate but also by chronically regulating food intake. We further speculate that high-fat diets produce obesity in part because carbohydrates are, per calorie, more effective than lipids to reduce food intake and increase metabolic rate. In support of this glucoadipostatic hypothesis, the 5 present review examines evidence that obesity and the metabolic syndrome may be due to reduction in neuroendocrine sensitivity to glucose leading to increased metabolic efficiency.
由于营养敏感反馈信号通常作用于维持可用营养资源和储存营养资源的相对稳定水平，这些反馈信号中的一个或多个出现故障可能会合理地导致肥胖表型。原始形式的葡萄糖稳态假说认为葡萄糖是一种生理饱腹感因子（即餐后血浆葡萄糖升高会导致进食终止），但这种形式的假说难以证明，尤其是自瘦素被发现以来，葡萄糖稳态假说在很大程度上已被摒弃。然而，血浆葡萄糖水平或葡萄糖信号的降低会产生与瘦素缺乏所产生的神经内分泌反应相似的特征。由于瘦素不是生理饱腹感因子（因为它在进食终止前不会升高），然而瘦素缺乏会导致肥胖，我们建议重新构建葡萄糖稳态假说，不涉及饱腹感（即对食物摄入的短期影响）。相反，我们认为与瘦素信号一样，葡萄糖信号调节长期能量平衡，部分是通过调节代谢率，也通过长期调节食物摄入量。我们进一步推测，高脂肪饮食导致肥胖部分是因为每卡路里的碳水化合物比脂质更有效地减少食物摄入并提高代谢率。为支持这种葡萄糖脂肪稳态假说，本综述研究了肥胖和代谢综合征可能是由于神经内分泌对葡萄糖的敏感性降低导致代谢效率提高的证据。
