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

基本信息

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
项目类别：
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

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

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项目摘要

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针对许多疾病的有效治疗形式。孕产妇运动，尤其是在怀孕期间，对童年的福祉产生了长期影响。这些有益效果的一部分来自称为运动的运动引起的激素的分泌。在锻炼和研究的同时随着药物的不断增长的锻炼，纵向量化运动效率的方法仍然是阐明。这项研究构建了使用代谢成像跟踪运动效率的工具和方法。我们假设小鼠运动将导致棕色脂肪组织的激活（BAT）。这个代谢可以使用超极化磁共振成像（HP-MRI）检测到激活。 HP-MRI是一种替代品 - 可以量化代谢通量的边缘代谢成像平台。惠普是一种提高灵敏度的方法非放射活性稳定的碳13标记的分子，例如[1-13c]丙酮酸。这提高了灵敏度可以检测丙酮酸转化率，并作为代谢的替代标志物进行渗透以及碳酸氢盐。因此，我们假设HP-MRI会因运动而实现对BAT激活的非侵入性检测 and exercise exposure. 在AIM 1中，我们在使用HP-MRI的小鼠运动模型中纵向跟踪BAT激活。我们开拓了 [1-13C]丙酮酸和二乙基[1-13C]-α-酮戊二酸酯（DE--kg）的两个不同的HP成像问题的发展。然后，我们将将HP-MRI与金标准等离子体锻炼进行比较，以确认代谢激活。在AIM 2中，我们将实验扩展到使用HP-MRI的后代。最后，我们问HP-MRI是否可以检测高脂，高果糖饮食挑战的后代的代谢变化。总之，我们的目标提供概念和技术创新，开创一种非侵入性成像方法，以研究在怀孕的母亲及其后代运动。为了确保成功，我们的研究团队包括生物化学，成像，成像，成像专业知识的独特组合和运动生物学。成功完成目标将对我们对在孕妇及其后代的长期影响，直到成年。