ACUTE AND CHRONIC CALORIE RESTRICTION AND THE METABOLIC SYNDROME

急性和慢性热量限制以及代谢综合征

• 批准号: 7603340
• 负责人: Dominic N Reeds
• 金额: $ 1.06万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603340
• 关键词: Acute; Affect; Biopsy; Blood Tests; Body Composition; Body Weight; Body Weight decreased; Body measure procedure; Caloric Restriction; Carbohydrates; Chronic; Computer Retrieval of Information on Scientific Projects Database; Coronary heart disease; Diet; Energy Intake; Fatty Acids; Fatty acid glycerol esters; Functional disorder; Funding; Gene Expression; Goals; Grant; Inflammation; Infusion procedures; Institution; Insulin; Insulin Resistance; Intake; Isotopes; Lead; Macronutrients Nutrition; Magnetic Resonance Spectroscopy; Metabolic; Metabolic syndrome; Modification; Muscle; Obesity; Pathogenesis; Patients; Randomized; Research; Research Personnel; Resources; Risk Factors; Source; Stable Isotope Labeling; Staging; Tracer; United States National Institutes of Health; Vascular Diseases; Week; day; dietary restriction; fatty acid metabolism; improved; insulin sensitivity; prevent

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. Insulin resistance is an underlying eature of the metabolic syndroe, and is associated with endothelial dysfunction and coronary heart disease. Weight loss improves insulin sensitivity, endothelial function, and all features of the metabolic syndrome in obese subjects. In addition, short-term calorie restriction, without significant weight loss, improves insulin action. However, the mechanism(s) responsible for the improvement in insulin action induced by acute calorie restriction, and whether a decrease in a specific macronutrient or total energy intake is responsible for the beneficial effects, are not known. Moreover, it is not known whether short-term calorie restriction improves endothelial function. Therfore, the primary goal of this project is to evaluate the potential mechanisms responsible for the effect of acute and chronic calorie restriction on two key factors involved in the pathogenesis of vascular disease, insulin sensitivity and inflammation, n subjects with the metabolic syndrome. We hypothesize that short-term caloric restriction affects insulin action by altering fatty acid metabolism and inflammation. More specifically, we hypothesize that calorie restriction with adequate carbohydrate intake (>=120 g/d) improves insulin action, inflammation, and endothelial function (a marker of vascular disease) while acute calorie restriction with low carbohydrate intake (<=40 g/d) will impair these parameters because of increased fatty acid flux. We also propose that moderate weight loss, whether induced by low-fat or low carbohydrate diets, will have greater beneficial effects on insulin action, inflammation and endothelial function that short-term caloric restriction because of long-term modification of gene expression. A better understanding of the mechanisms responsible for the effect of acute and chronic energy restriction on metabolic risk factors for vascular disease could lead to more effective treatment strategies for obese patients who have the metabolic syndrome. Forty (BMI 30-45 kg/ms) subjects will be randomize to receive a hypocaloric diet with either adequate (>=120 g/d) or low (<=40 g/d) carbohydrate content. The diet will provide a 50% calorie deficit with pre and pose measures of body composition, two-stage euglycemic hyperinsulinemic clamp with stable isotope labeled tracer infusion, magnetic resonance spectroscopy (MRS), and muscle biopsies. Following the two days of acute caloric restriction subjects will continue the same 50% kcal restricted diet untile they lose 5% of their initial body weight. Once subjects have achieved a 5% body weight loss, their total calorie intake will be adjusted to maintain constant body wieght and prevent further body loss. After subjects have maintained 5% weight loss for approximately 3 weeks, body composition analyses, baseline blood tests, and the isotope infustion study will be repeated.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 胰岛素抵抗是代谢综合征的潜在特征，并且与内皮功能障碍和冠心病相关。 减肥可改善肥胖受试者的胰岛素敏感性、内皮功能和代谢综合征的所有特征。 此外，短期热量限制在不显着减轻体重的情况下可以改善胰岛素作用。 然而，由急性热量限制引起的胰岛素作用改善的机制，以及特定常量营养素或总能量摄入的减少是否会产生有益效果，尚不清楚。 此外，尚不清楚短期热量限制是否可以改善内皮功能。 因此，该项目的主要目标是评估急性和慢性热量限制对代谢综合征受试者中涉及血管疾病发病机制的两个关键因素（胰岛素敏感性和炎症）产生影响的潜在机制。 我们假设短期热量限制通过改变脂肪酸代谢和炎症来影响胰岛素的作用。 更具体地说，我们假设通过充足的碳水化合物摄入量（>=120克/天）进行热量限制可以改善胰岛素作用、炎症和内皮功能（血管疾病的标志），而通过低碳水化合物摄入量（<=40克/天）进行急性热量限制可以改善胰岛素作用、炎症和内皮功能（血管疾病的标志）。 d) 由于脂肪酸通量增加，会损害这些参数。 我们还提出，由于基因表达的长期改变，适度的体重减轻，无论是由低脂肪还是低碳水化合物饮食引起，都会比短期热量限制对胰岛素作用、炎症和内皮功能产生更大的有益影响。 更好地了解急性和慢性能量限制对血管疾病代谢危险因素影响的机制可能会为患有代谢综合征的肥胖患者提供更有效的治疗策略。 四十名（BMI 30-45 kg/ms）受试者将随机接受碳水化合物含量充足（>=120 g/d）或低（<=40 g/d）碳水化合物含量的低热量饮食。 该饮食将提供 50% 的卡路里赤字，并进行身体成分测量、两阶段血糖正常高胰岛素钳夹和稳定同位素标记示踪剂输注、磁共振波谱 (MRS) 和肌肉活检。 在两天的急性热量限制之后，受试者将继续相同的 50% kcal 限制饮食，直到他们减掉初始体重的 5%。 一旦受试者体重减轻 5%，他们的总卡路里摄入量将被调整，以维持恒定的体重并防止进一步的体重减轻。 在受试者保持 5% 的体重减轻约 3 周后，将重复进行身体成分分析、基线血液测试和同位素输注研究。