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.

项目总结/摘要 运动越来越被视为治疗许多疾病的有效形式。母亲锻炼， 特别是在怀孕期间，对儿童的健康有长期的影响。这些有益效果的一部分 来自运动引起的荷尔蒙分泌，称为运动因子。虽然研究运动和 运动因子随着药物的不断发展，纵向量化运动功效的方法仍有待进一步研究。 阐明。这项研究建立了使用代谢成像跟踪运动功效的工具和方法。 我们假设小鼠的运动会导致棕色脂肪组织（BAT）的激活。这种代谢 可以使用超极化磁共振成像（HP-MRI）检测激活。HP-MRI是一种切割- 边缘代谢成像平台，可以量化代谢通量。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- 13 C]丙酮酸。这增加了敏感性 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记。 因此，我们假设HP-MRI将能够无创检测由于运动引起的BAT激活 和运动因子暴露。 在目标1中，我们使用HP-MRI在小鼠运动模型中纵向跟踪BAT激活。我们开拓了 开发了两种不同的HP成像探针，[1- 13 C]丙酮酸盐和二乙基-[1- 13 C]-α-酮戊二酸盐（DE-β-KG）。 然后，我们将比较HP-MRI与金标准血浆运动因子测量，以确认代谢 activation. 在目标2中，我们将实验扩展到在运动小鼠的后代中使用HP-MRI。最后，我们问HP-MRI是否 可以检测到后代在高脂肪、高果糖饮食下的代谢变化。我们的目标 提供概念和技术创新，开创了一种非侵入性成像方法，以研究 孕妇和她们的孩子。 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。成功地完成这些目标将对我们理解 长期影响的运动，在怀孕的母亲和他们的后代，直到成年。