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.

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