SUBSTRATE REGULATION DURING ENERGY DEFICIT IN OBESITY

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 最近的估计表明，美国近三分之二的成年人超重或肥胖。尽管数百万人试图减肥，但肥胖症的流行率继续以惊人的速度增加。 减肥需要摄入的卡路里比消耗的卡路里少（即;能量赤字），但人们对识别和应对能量赤字的机制知之甚少。 人体对碳水化合物可用性的降低非常敏感，并且已知影响能量代谢的主要激素反应主要受碳水化合物可用性的变化而不是膳食脂肪的影响。 在没有碳水化合物可用性变化的情况下“感知”能量可用性减少的机制还没有很好的定义。因此，识别人体响应和适应能量缺乏的机制本身可以导致改善肥胖症的饮食和/或药物治疗。 我们的第一个目的是评估当摄入低热量低脂肪饮食时，胃肠道对脂质和蛋白质代谢调节的参与。 我们将测量腹部肥胖男性和女性（I类和II类肥胖）在体重维持饮食后以及通过将脂肪摄入量降低至<5g/天诱导的40%能量不足2天后的脂解、葡萄糖摄取、蛋白质降解和蛋白质合成。在第三次访视时，受试者将摄入低脂饮食2天，但我们将通过静脉输注脂质（绕过胃肠道）来防止能量不足。我们的第二个目标是确定新的肽释放骨骼肌和脂肪组织在响应低热量低脂肪饮食。 我们的总体假设是，低脂肪饮食的能量不足主要是在胃肠道“感觉”到的。 这引发了一系列信号，刺激代谢过程，如脂肪分解和蛋白水解，同时减少蛋白质合成。 然而，我们也相信新的外周因子从脂肪组织和骨骼肌释放，以增加对全身能量可用性的代谢反应。 这项研究的结果将确定参与感知和响应能量不足的机制，这对于开发改进的减肥药理学和饮食治疗至关重要。'

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent estimates indicate that nearly two-thirds of all adults in the United States are overweight or obese. Despite attempts by millions of people to lose weight the prevalence of obesity continues to increase at an alarming rate. Weight-loss requires that fewer calories be ingested than expended (i.e.; energy deficit), but the mechanisms that recognize and respond to energy deficit are poorly understood. The human body is very sensitive to a reduced availability of carbohydrate, and the major hormonal responses known to affect energy metabolism are primarily influenced by changes in carbohydrate availability rather than dietary fat. The mechanisms that "sense" a reduction in energy availability, without a change in carbohydrate availability are not well defined. Accordingly, identifying mechanisms by which the human body responds and adapts to energy deficit, per se, could lead to improved dietary and/or pharmacological treatments for obesity. Our first aim is to evaluate the involvement of the gastrointestinal tract on the regulation of lipid and protein metabolism when ingesting a low calorie-low fat diet. We will measure lipolysis, glucose uptake, protein degradation, and protein synthesis in abdominally obese men and women (Class I and II obesity) after a weight-maintenance diet and again after 2 days of a 40% energy deficit, induced by lowering fat intake to <5g/day. On a third visit, subjects will ingest the low-fat diet for 2 days but we will prevent an energy deficit by infusing lipids intravenously, by-passing the gastrointestinal tract. Our second aim is to identify novel peptides released from skeletal muscle and adipose tissue in response to a low calorie-low fat diet. Our overall hypothesis is that the energy deficit from a low-fat diet is primarily "sensed" in the gastrointestinal tract. This initiates a cascade of signals that stimulate metabolic processes such as lipolysis and proteolysis, while reducing protein synthesis. However, we also believe that novel peripheral factors are released from adipose tissue and skeletal muscle to augment the metabolic response to systemic energy availability. The findings from this study will identify mechanisms involved in sensing and responding to energy deficit, which is critical for the development of improved pharmacological and dietary treatments for weight-loss.'