The role of mitochondrial metabolism in weight loss

线粒体代谢在减肥中的作用

• 批准号: 10673135
• 负责人: Ana Patricia Valencia
• 金额: $ 12.74万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673135
• 关键词: Acceleration; Address; Adherence; Animals; Area; Arterial Fatty Streak; Atherogenic Diet; Atherosclerosis; Basic Science; Behavioral; Bioenergetics; Biological; Biology; Body Composition; Body Weight decreased; CCL2 gene; Carbohydrates; Cardiovascular Diseases; Cell Separation; Cells; Clinical; Clinical Research; Data; Diet; Dyslipidemias; Energy Metabolism; Exposure to; Fatty Acids; Fatty acid glycerol esters; Foundations; Funding; Future; Genetic; Goals; Hepatocyte; Human; Immune; In Vitro; Indirect Calorimetry; Individual; Inflammation; Institution; Insulin Resistance; Interleukin-10; Interleukin-6; Knowledge; Learning; Life Style; Link; Lipids; Liver; Magnetic Resonance; Measures; Mediating; Mentorship; Metabolic; Metabolism; Mitochondria; Monocytosis; Mononuclear; Mus; Muscle; Muscle Cells; Muscle Mitochondria; Neutrophilia; Obesity; Oxidants; Oxidation-Reduction; Participant; Peripheral; Persons; Phase; Predisposition; Production; Recommendation; Relapse; Research; Research Activity; Resistance; Respiration; Risk; Risk Factors; Rodent; Rodent Model; Role; Sampling; Serum; Skeletal Muscle; Stress; System; T-Lymphocyte; TNF gene; Techniques; Testing; Therapeutic; Thinness; Time; Tissues; Training; Translational Research; United States National Institutes of Health; Weight; Weight maintenance regimen; analytical tool; cardiometabolic risk; cardiovascular disorder risk; cardiovascular risk factor; career; career development; cell type; diet-induced obesity; experience; experimental study; healthy weight; human model; insight; insulin sensitivity; lonely individuals; metabolic phenotype; mitochondrial dysfunction; mitochondrial metabolism; monocyte; mouse model; novel; nutrition; oxidation; prevent; programs; protein expression; respiratory; response; weight maintenance

PROJECT SUMMARY Obesity is a major risk factor for cardiovascular (CV) disease. Various CV risk factors like insulin resistance, dyslipidemia, and inflammation are associated with mitochondrial dysfunction. Weight loss is the main recommendation to reduce cardiometabolic risk for people with obesity, but the protection is proportional to the magnitude of weight lost, and fades over time during weight maintenance with the reversal or worsened risk in those who regain weight. This proposal aims to investigate mitochondrial adaptations with weight loss that might lessen its capacity to protect against CV disease. We will do this by studying adaptation in the plateau phase, a time period when further weight loss becomes minimal despite efforts to continue losing weight, and weight regain often follows. The plateau phase is currently understudied and links the occurrence of a weight loss plateau with diminished protection against cardiometabolic risk. In AIM 1, I will determine functional differences in mitochondria at the weight loss plateau in immune cells isolated from people with obesity undergoing weight loss. In AIM 2, I will develop paradigms of the plateau- state in mice with diet-induced obesity to test whether reduced mitochondrial respiratory capacity in liver muscle and immune cells is an underlying mechanism for adaptation in energy expenditure (metabolic adaptation) at the plateau that promote weight regain. For AIM 3, I will determine in a mouse model of accelerated atherosclerosis whether mice the plateau state develop more severe diet-induced CMR, atherosclerosis, and immune cell redox stress. This proposal will be carried out in an institution with strong research programs in metabolism, obesity, and cardiovascular disease. I will receive state-of-the-art training in techniques and analytical tools necessary for completion of all aims, including clinical samples from NIH-funded obesity studies, indirect calorimetry in rodents, and assessment of atherogenic risk in mice. This proposal will generate data laying the foundation for my independent research career focused on mitochondrial mechanisms that influence cardiometabolic risk in obesity.

项目总结