Longitudinal Imaging of Maternal Exercise and Exerkine Effects on Offspring Metabolism

母亲运动的纵向成像和 Exerkine 对后代代谢的影响

• 批准号: 10726363
• 负责人: Junseok Son
• 金额: $ 23.18万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10726363
• 关键词: 3-Dimensional; APLN gene; Adult; Affect; Bicarbonates; Biochemistry; Biology; Brown Fat; Carbon; Cells; Child Health; Childhood; Citric Acid Cycle; Clinical Trials; Contrast Media; Data; Detection; Development; Diet; Disease; Ensure; Epigenetic Process; Exercise; FAT3 gene; Fatty acid glycerol esters; Fetal Development; Fructose; Gene Modified; Goals; Grant; Half-Life; Health; Health Status; Hormones; Image; Imaging Techniques; Imaging technology; Isotopes; Label; Life; Liver; Long-Term Effects; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maryland; Maternal Health; Measurement; Measures; Mediating; Medicine; Metabolic; Metabolic Activation; Metabolism; Methods; Modality; Mothers; Mus; Muscle; Non-Invasive Detection; Organ; Outcome; Personal Satisfaction; Physical Exercise; Physiologic pulse; Placentation; Plasma; Positron-Emission Tomography; Pregnancy; Pregnant Women; Pyruvate; Radioactive; Research; Scanning; Signal Transduction; Supplementation; Surrogate Markers; Techniques; Technology; Testing; Therapeutic; Three-Dimensional Imaging; Tissues; Translations; Universities; Uterus; Water; Work; alpha ketoglutarate; combat; diet-induced obesity; effective therapy; experimental study; fetal; frailty; healthspan; imaging modality; imaging platform; imaging probe; in vivo; indexing; innovation; mass spectrometric imaging; metabolic imaging; metabolomics; minimally invasive; mouse model; non-invasive imaging; offspring; pregnant; protective effect; sedentary; serial imaging; success; tool; western diet; whole body imaging

Project Summary/Abstract Exercise is increasingly being seen as an effective form of therapy against many diseases. Maternal exercise, especially during pregnancy, has long-lasting effects on childhood wellbeing. Part of these beneficial effects come from the secretion of exercise-induced hormones called exerkines. While research into exercise and exerkines as medicines continue to grow, methods to longitudinally quantify exercise efficacy remain to be elucidated. This research builds tools and methods to track exercise efficacy using metabolic imaging. We hypothesize that exercise in mice will result in activation of brown adipose tissue (BAT). This metabolic activation can be detected using hyperpolarized magnetic resonance imaging (HP-MRI). HP-MRI is a cutting- edge metabolic imaging platform that can quantify metabolic flux. HP is a method that increases the sensitivity of non-radioactive, stable carbon-13 labeled molecules, such as [1-13C] pyruvate. This increased sensitivity enables detection of pyruvate conversion to lactate, as well as bicarbonate as surrogate markers of metabolism. Therefore, we hypothesize that HP-MRI will enable non-invasive detection of BAT activation, due to exercise and exerkine exposure. In Aim 1, we longitudinally track BAT activation in a mouse model of exercise using HP-MRI. We pioneer the development of two different HP imaging probes, [1-13C] pyruvate and diethyl-[1-13C]-α-ketoglutarate (DE--KG). We will then compare HP-MRI with gold-standard plasma exerkine measurements, to confirm metabolic activation. In Aim 2, we extend our experiments to use HP-MRI in offspring of exercised mice. Finally, we ask if HP-MRI can detect metabolic changes in offspring challenged with high-fat, high-fructose diets. Taken together, our Aims provide conceptual and technical innovation, pioneering a non-invasive imaging method to study the effects of exercise in pregnant mothers and their offspring. To ensure success, our research team consists of a unique combination of expertise in biochemistry, imaging, and exercise biology. Successful completion of the aims will have a major impact on our understanding of the long term effects of exercise, in both pregnant mothers and their offspring, well into adulthood.

项目摘要/摘要 运动越来越被视为对抗多种疾病的一种有效疗法。母性锻炼， 尤其是在怀孕期间，对儿童的健康有长期的影响。这些有益影响的一部分 来自一种叫做激动素的运动诱导荷尔蒙的分泌。在研究锻炼和 随着药物的不断发展，纵向量化运动效果的方法仍有待改进 已澄清。这项研究建立了使用代谢成像跟踪运动效果的工具和方法。 我们假设，小鼠的运动将导致棕色脂肪组织(BAT)的激活。这种新陈代谢 激活可以使用超极化磁共振成像(HP-MRI)来检测。HP-MRI是一种尖端的- EDGE代谢成像平台，可量化代谢流量。HP是一种提高灵敏度的方法 非放射性、稳定的碳-13标记分子，如[1-13C]丙酮酸。这增加了敏感度 能够检测丙酮酸转化为乳酸，以及碳酸氢盐作为代谢的替代标志物。 因此，我们假设HP-MRI将能够非侵入性地检测由于运动引起的BAT激活 以及令人疲惫的暴露。 在目标1中，我们使用HP-MRI纵向跟踪运动小鼠模型中蝙蝠的激活。我们开创了 两种不同的HP成像探针，[1-13C]丙酮酸和[1-13C]-α-酮戊二酸二乙酯(DE--KG)的研制。 然后，我们将把HP-MRI与金标准血浆运动测量进行比较，以确认代谢 激活。 在目标2中，我们将我们的实验扩展到在运动小鼠的子代中使用HP-MRI。最后，我们询问HP-MRI是否 可以检测到接受高脂肪、高果糖饮食挑战的后代的代谢变化。总而言之，我们的目标 提供概念和技术创新，开创了非侵入性成像方法来研究 孕妇及其子代的运动。 为了确保成功，我们的研究团队由生物化学、成像、 和运动生物学。这些目标的顺利完成将对我们理解 运动的长期影响，无论是对怀孕的母亲还是她们的后代，一直持续到成年。