Impact of Time-Restricted Feeding (TRF) on Glucose Homeostasis and Mitochondrial Function in Patients with Metabolic Syndrome

限时喂养 (TRF) 对代谢综合征患者血糖稳态和线粒体功能的影响

• 批准号: 9977002
• 负责人: Pam Rajendran Taub
• 金额: $ 70.05万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977002
• 关键词: Adopted; Adult; Animal Model; Animals; Behavioral; Bioenergetics; Biological; Biological Markers; Biological Rhythm; Biopsy; Blood Glucose; Body Composition; Calories; Cardiovascular Diseases; Cardiovascular system; Cellular Phone; Chronic; Circadian Dysregulation; Circadian Rhythms; Clinical Research; Consumption; Control Groups; Counseling; Data; Diabetes Mellitus; Diagnosis; Diet; Dietary Intervention; Disease; Disease Progression; Doctor of Philosophy; Dual-Energy X-Ray Absorptiometry; Dyslipidemias; Eating; Equilibrium; Experimental Designs; Fasting; Food; Gene Expression; Genes; Glucose; Glycosylated hemoglobin A; Health; Homeostasis; Hour; Human; Impairment; Individual; Inflammation; Institutes; Insulin Resistance; Intake; Intervention; Life Style; Low-Density Lipoproteins; Medicine; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolic syndrome; Metabolism; Methods; Mitochondria; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Obesity; Participant; Patients; Pattern; Play; Prevention; Principal Investigator; Process; Proteins; Psychiatry; Publishing; Randomized; Randomized Controlled Trials; Regulation; Research Personnel; Risk; Rodent; Role; Scanning; Skeletal Muscle; Sleep; Stress; Structure; Testing; Therapeutic; Time; Time-restricted feeding; United States; abdominal fat; blood glucose regulation; cardiometabolism; cardiovascular risk factor; compliance behavior; feeding; glucose monitor; group intervention; improved; lifestyle intervention; light microscopy; novel strategies; nutrition; particle; pre-clinical; prevent; primary endpoint; response; smartphone Application; standard of care

Project Abstract In the United States, about 34% of adults meet criteria for metabolic syndrome, which is characterized by the presence of multiple risk factors for cardiovascular disease and diabetes. Diet and lifestyle interventions are critical to prevent disease progression in patients with type II-diabetes mellitus and cardiometabolic disease. However, patient adherence is low with existing interventions that focus on changing the quality and quantity of nutrition and activity. Thus, a new method of prevention and treatment is greatly needed. Recent studies have shown that the timing of eating also plays a large role in metabolism. Circadian rhythms optimize nutrient homeostasis by orchestrating daily rhythms in catabolic and anabolic metabolism to appropriate time during the 24-hour day. Chronic circadian rhythm disruption due to lifestyle including erratic eating patterns predisposes individuals to metabolic diseases including type 2 diabetes and obesity. In rodents, 8-12 h of time-restricted feeding without altering calorie consumption or food composition can prevent and reverse diet-induced obesity and its associated metabolic dysfunction. Consequently, the diurnal regulation of metabolism through alternating periods of feeding and fasting offers a promising avenue for the prevention and treatment of metabolic disease. The major objective of this proposal is to determine the efficacy of restricting daily calorie intake to a reduced/fixed number of hours per day (time-restricted feeding, TRF) to improve metabolic health. We will achieve this with the following specific aims: 1) Evaluate the impact of TRF on glucose homeostasis with exploratory aims to assess changes in mitochondrial structure and gene expression in skeletal muscle and 2) Assess the changes in metabolic biomarkers in response to TRF. 3) Assess the impact of TRF on body composition. In this study, we will ask participants who have been diagnosed with metabolic syndrome to restrict their food intake to 10 hours a day and fast for 14 hours for 12-weeks. Eating, sleeping, and activity patterns will be assessed throughout the study with a smartphone app. Sleeping and activity patterns will also be observed with actiwatches for one week at baseline and one week at the end of the study. Glucose homeostasis, metabolic biomarkers, and body composition will be assessed at baseline and at the end of the TRF intervention. In addition, we will conduct skeletal muscle biopsies to assess the changes in mitochondrial structure by light microscopy and in critical proteins that regulate mitochondrial function. We hypothesize that imposing feeding- fasting cycles (TRF) will restore the equilibrium between catabolic and anabolic processes, which will improve glucose homeostasis and cardiometabolic biomarkers, decrease abdominal fat, and enhance mitochondrial function.

项目摘要 在美国，约有34％的成年人符合代谢综合征标准，其特征是 存在多种心血管疾病和糖尿病的危险因素。饮食和生活方式干预是 对于预防II型糖尿病和心脏代谢疾病患者的疾病进展至关重要。 但是，患者的依从性低于现有干预措施，重点是改变质量和数量 营养和活动。因此，非常需要一种新的预防和治疗方法。最近的研究 表明饮食时机在代谢中也起着很大的作用。昼夜节律优化养分 通过在分解代谢和合成代谢代谢中的每日节奏进行适当的时间进行适当的时间来稳态 24小时的一天。由于生活方式而导致的慢性昼夜节律破坏，包括不稳定的饮食方式 个体患有代谢性疾病，包括2型糖尿病和肥胖症。在啮齿动物中，时间限制为8-12 h 进食而不改变卡路里消耗或食物成分可以预防和逆转饮食诱导的肥胖症 及其相关的代谢功能障碍。因此，通过交替对代谢的昼夜调节 喂养和禁食期为预防和治疗代谢疾病提供了有希望的途径。 该提案的主要目的是确定将每日卡路里摄入量限制为 减少/固定的每天小时数（限制时间喂养，TRF）以改善代谢健康。我们将 通过以下特定目的实现此目的：1）评估TRF对葡萄糖稳态的影响 探索性旨在评估骨骼肌中线粒体结构和基因表达的变化和2） 评估响应TRF的代谢生物标志物的变化。 3）评估TRF对身体的影响 作品。在这项研究中，我们将要求被诊断为代谢综合征的参与者限制 他们的食物摄入量至每天10个小时，而12周的食物摄入量为14小时。进食，睡眠和活动方式将 在整个研究中都可以使用智能手机应用程序进行评估。还将观察到睡眠和活动方式 在研究结束时，在基线时进行了一个星期的Actiwatches，并进行了一周的时间。葡萄糖稳态，代谢 生物标志物和身体成分将在基线和TRF干预结束时进行评估。在 此外，我们将进行骨骼肌活检以评估线粒体结构的变化 显微镜和调节线粒体功能的关键蛋白质。我们假设施加喂养 - 禁食周期（TRF）将恢复分解代谢过程和合成代谢过程之间的平衡，这将改善 葡萄糖稳态和心脏代谢生物标志物，减少腹部脂肪并增强线粒体 功能。