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)是一种用于治疗难治性癫痫的高脂肪低碳水化合物饮食，正变得越来越多。 受欢迎的体重管理，它可以潜在地减缓认知老化和缓解症状 神经疾病，如中风、帕金森氏病和老年痴呆症。然而，KD也会导致骨质流失 并增加儿童骨折的风险。目前尚不清楚KD是否会导致成年人的骨质流失。基于先前的研究， KD也有可能降低运动增加骨骼强度的能力。其作用机制 对KD骨丢失负有责任的人尚未确定。确定β-羟基丁酸酯(BHb)是否最 丰富的酮体与骨质流失有关是很重要的，因为这种分子被认为在 KD的神经学益处。该项目将使用小鼠模型来评估生酮的年龄差异。 饮食导致骨丢失，确定KD是否降低了锻炼使骨骼强壮的能力，并进行了调查 如果BHB导致骨质流失。 目标1将确定年龄和饮食持续时间如何影响KD引起的骨丢失的幅度和 骨骼强度下降。目标2将评估KD是否降低了锻炼以增加骨骼强度的能力 如果这是由肌肉和肌腱调节的。目标3将特别侧重于确定BHB在骨骼中的作用 损失。从长远来看，这个项目将有助于阐明KD如何影响骨骼，并有助于KD或KD的使用 补充高铁血红蛋白，在不增加骨折风险的情况下提供神经益处。 作为一名临床研究人员，我努力开发改善骨骼健康的疗法，作为一名生物学家 人类学家，我用骨骼遗骸来重建过去人们的行为和健康。通过 K99/R00职业发展奖，我寻求将我的人类学和生物医学结合起来 通过研究生酮饮食和运动对终生骨骼健康的综合影响来进行研究。 在奖学金期间，我将接受分子生物学和实验室技能方面的培训，这些技能是学习 细胞对饮食和运动的反应。我还将扩大我对肌肉和肌腱的知识，获得能力 进行创新的跨学科研究，以新的视角研究运动和饮食的影响 骨骼强度。加州大学戴维斯分校是开展拟议项目和培训的无与伦比的地点。我要一杯 获得最先进的设施和设备。通过大量的研讨会、研讨会和培训 机会，我将与教职员工、学生和工作人员互动，扩大我对骨骼健康的理解。 通过K99/R00，我将发展一个创新的跨学科研究生涯，探索两者之间的关系 在过去的人类人群中饮食、行为和健康之间的关系，并有助于治疗的发展 通过饮食和锻炼来降低骨折风险。