Age Differences and Mechanisms of Ketogenic Diet Induced Bone Loss

生酮饮食导致骨质流失的年龄差异和机制

• 批准号: 10740305
• 负责人: Benjamin Osipov
• 金额: $ 8.59万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740305
• 关键词: Adult; Advisory Committees; Affect; Age; Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Animal Model; Animals; Automobile Driving; Behavior; Biological; Body Weight decreased; Bone Matrix; Bone Resorption; Bone Tissue; Bone remodeling; Bone structure; C14 isotope; Carbohydrates; Chemicals; Child; Clinical; Clinical Research; Cognitive aging; Diet; Educational workshop; Elements; Epilepsy; Equipment; Esters; Exercise; Faculty; Fatty acid glycerol esters; Fellowship; Gene Expression; Gene Expression Regulation; Health; High Fat Diet; Hormones; Human; Inflammation; Insulin-Like Growth Factor I; Interdisciplinary Study; Intervention; Intractable Epilepsy; K-Series Research Career Programs; Ketone Bodies; Ketones; Knock-out; Knowledge; Label; Laboratories; Life; Ligands; Link; Location; Longevity; Measures; Mechanical Stimulation; Mediating; Metabolism; Molecular Biology; Mus; Muscle; Neurologic; Nicotinic Acids; Organ; Osteoblasts; Osteoclasts; PTH gene; Parkinson Disease; Pathway interactions; Persons; Play; Population; Process; Protein Biosynthesis; Public Health; Recovery; Reducing diet; Research; Research Personnel; Role; Route; Serum; Signal Transduction; Skeletal system; Stroke; Structure; Students; Supplementation; Tendon structure; Testing; Therapeutic; Time; Training; Up-Regulation; Vitamin D; Weight maintenance regimen; age difference; age effect; beta-Hydroxybutyrate; bone; bone cell; bone health; bone loss; bone mass; bone strength; bone turnover; career; clinically significant; cytokine; diet and exercise; dietary control; fracture risk; human old age (65+); improved; innovation; interest; ketogenic diet; mature animal; mechanical properties; middle age; mouse model; nervous system disorder; osteogenic; pre-clinical; prevent; receptor; reduce symptoms; response; skeletal; skills; slow potential; therapy development; training opportunity; treadmill; young adult

Project Summary Ketogenic diet (KD), a high fat low carbohydrate diet is used to treat intractable epilepsy, is becoming increasingly popular for weight management, and it can potentially slow cognitive ageing and alleviate symptoms of neurological disorders such as stroke, Parkinsons disease, and Alzheimers. However, KD also causes bone loss and increases fracture risk in children. It is not known if KD causes bone loss in adults. Based on prior studies, it is also possible that KD may reduce the ability for exercise to increase bone strength. The mechanisms responsible for KD bone loss have not been identified. Determining if β-hydroxybutyrate (BHB), the most abundant ketone body is linked to bone loss is important, because this molecule is thought to lay a large role in the neurological benefits of KD. This project will use a mouse model to evaluate age differences in ketogenic diet induced bone loss, determine if KD decreases the ability of exercise to make bone stronger, and investigate if BHB causes bone loss. Aim 1 will determine how age and diet duration affect the magnitude of KD induced bone loss and decrease in bone strength. Aim 2 will evaluate if KD reduces the ability of exercise to increase bone strength and if this is mediated by muscle and tendon. Aim 3 will focus specifically on defining the role of BHB in bone loss. In the long term, this project will help clarify how KD affects bone, and it can contribute to the use of KD or BHB supplementation to deliver neurological benefits without increasing fracture risk. As a clinical researcher, I strive to develop therapies to improve skeletal health, and as a biological anthropologist, I use skeletal remains to reconstruct the behavior and health of past people. Through the K99/R00 career development award, I seek to combine the anthropological and biomedical strands of my research career by examining the combined effect of ketogenic diet and exercise on bone health throughout life. During the fellowship, I will receive training in molecular biology and laboratory skills essential for the study of cellular responses to diet and exercise. I will also expand my knowledge of muscle and tendon, gaining the ability to conduct innovative interdisciplinary research that achieves new perspectives on how exercise and diet affect bone strength. UC Davis is an unparalleled location for conducting the proposed project and training. I will have access to cutting edge facilities and equipment. Through numerous seminars, workshops, and training opportunities I will interact with faculty, students, and staff, broadening my understanding of skeletal health. Through the K99/ R00 I will develop an innovative interdisciplinary research career that explores the relationship between diet, behavior, and health in past human populations and contributes to the development of therapies that use diet and exercise to decrease fracture risk.

项目摘要 生酮饮食（KD）是一种高脂肪低碳水化合物饮食来治疗顽固性癫痫病，越来越多 在体重管理方面很受欢迎，它可能会缓慢地认知衰老并减轻 神经系统疾病，例如中风，帕金森氏病和阿尔茨海默氏症。但是，KD也会导致骨质流失 并增加儿童骨折风险。尚不清楚KD是否会导致成年人的骨质流失。基于先前的研究， KD也可能会降低运动增加骨骼强度的能力。机制 尚未确定负责KD骨质流失。确定β-羟基丁酸（BHB）是否是最多的 最富有的酮体与骨质流失有关很重要，因为该分子被认为在 KD的神经系统益处。该项目将使用鼠标模型来评估年龄差异 饮食引起的骨质流失，确定KD是否会降低运动能使骨骼更强壮的能力，并调查 如果BHB导致骨质流失。 AIM 1将确定年龄和饮食持续时间如何影响KD诱导的骨质流失和 骨骼强度降低。 AIM 2将评估KD是否会降低运动增加骨骼强度的能力 如果这是由肌肉和肌腱介导的。 AIM 3将专门针对定义BHB在骨骼中的作用 损失。从长远来看，该项目将有助于阐明KD如何影响骨骼，并且可以有助于使用KD或 补充BHB以提供神经系统益处，而不会增加骨折风险。 作为临床研究人员，我努力开发疗法以改善骨骼健康，并作为生物学 人类学家，我使用骨骼遗物来重建过去的人的行为和健康。通过 K99/R00职业发展奖，我试图结合我的人类学和生物医学链 研究职业通过检查生酮饮食和运动对骨骼健康一生的综合影响。 在奖学金期间，我将获得研究分子生物学和实验室技能的培训 细胞对饮食和运动的反应。我还将扩大对肌肉和肌腱的了解，获得能力 进行创新的跨学科研究，以实现有关运动和饮食如何影响的新观点 骨骼强度。加州大学戴维斯分校是进行拟议项目和培训的无与伦比的位置。我会的 进入最前沿的设施和设备。通过众多的半手，讲习班和培训 我将与教师，学生和员工互动的机会，扩大我对骨骼健康的理解。 通过K99/ R00，我将开发创新的跨学科研究职业，探索这种关系 在过去的人口中的饮食，行为和健康之间，并有助于疗法的发展 使用饮食和运动来降低断裂风险。