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Sex differences in cardiometabolic health of offspring born from obese mothers with and without exercise

肥胖母亲运动与不运动所生后代心脏代谢健康的性别差异

基本信息

批准号：
10612747
负责人：
Eunhee Chung
金额：
$ 37.5万
依托单位：
UNIVERSITY OF TEXAS SAN ANTONIO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-07 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10612747
关键词：
Address Adult Age Antioxidants Attenuated Biogenesis Biological Body Weight Cardiac Cardiometabolic Disease Cardiomyopathies Cardiovascular Diseases Cardiovascular system Child Chronic Disease Conceptions Data Diabetes Mellitus Diet Echocardiography Environment Epidemic Exercise Exhibits Exposure to Extracellular Matrix Female Fetal Heart Fibrosis Gene Expression Genes Genetic Transcription Glucose Intolerance Goals Health Heart Heart Diseases Heart Hypertrophy Histology Impairment In Vitro Individual Inherited Insulin Resistance Intervention Knowledge Lipids Measurement Measures Messenger RNA Metabolic Metabolic syndrome Mission Mitochondria Mitochondrial Diseases Modeling Molecular Morphology Mothers Mus Muscle Cells Myocardial dysfunction Myocardium Non-Insulin-Dependent Diabetes Mellitus Obesity Overweight Oxidative Stress Pathologic Population Predisposition Pregnancy Preparation Prevalence Production Property Proteins Public Health Publishing Respiratory physiology Role Sex Differences Structure System Testing Therapeutic Tissues United States National Institutes of Health Visualization Weaning Weight Woman cardiometabolism cardiovascular risk factor coronary fibrosis diet and exercise enzyme activity fetal heart function hemodynamics high risk improved in vivo interstitial intrauterine environment male maternal obesity mitochondrial dysfunction mitochondrial permeability transition pore obese mothers obesity in children obesogenic offspring pandemic disease pregnant prepregnancy prevent reproductive response sex

项目摘要

Project Summary/Abstract Obesity is a global epidemic; nearly 60% of women of reproductive age are considered overweight or obese in the U.S., and this percentage is continuously rising. The prevalence of childhood obesity is increasing at alarming rates, and children born from obese mothers have higher risks of developing diabetes, metabolic syndrome, and cardiovascular diseases. Compelling evidence from various species indicates that maternal obesity negatively influences the metabolic health of offspring and impacts various systems; however, there is a limited study investigating cardiac dysfunction of offspring born from obese mothers. Cardiomyopathy associated with mitochondrial disease occurs in 20-40% of children, and mitochondrial dysfunction is more prevalent in obese children than normal weight children. Unfortunately, the cellular and molecular mechanisms remain poorly understood. The long-term goal of this study is to determine the lifelong effects and mechanisms of an underlying abnormal maternal metabolic environment on cardiometabolic diseases in offspring and provide evidence for therapeutic strategy for preventing childhood obesity through maternal exercise. We have recently established pre-pregnancy and gestational obesity model in female mice in which the male offspring developed glucose intolerance and insulin resistance to a greater extent than female offspring. To address sex as a biological variable, both male and female offspring will be used to: 1) evaluate in vivo and in vitro contractile properties of the heart in response to maternal obesity with and without exercise; 2) determine morphological/structural alterations and gene expression of the heart born from obese mothers with and without exercise; and 3) determine oxidative stress and the mitochondrial function as the underlying mechanisms of maternal obesity and exercise on altered cardiometabolic health of offspring. Although the long-term beneficial effect of exercise on cardiac function is well documented in healthy normal weight population, to the best of our knowledge, our study is the first study to investigate the role of maternal exercise on cardiac function of offspring and the underlying mechanisms emphasizing on sex differences on mitochondrial function. The results of this proposed study will advance our knowledge of how maternal exercise modifies the cardiac structure, mitochondrial function, and overall heart function; and thus, could provide a new intervention for preventing heart disease associated with childhood obesity. Our proposal is well aligned with NIH’s mission to reduce the burden of chronic diseases.

项目概要/摘要肥胖是一种全球流行病；近 60% 的育龄妇女被认为超重或肥胖美国，而且这个比例还在不断上升。儿童肥胖症的患病率在逐年增加惊人的比率，肥胖母亲所生的孩子患糖尿病、代谢性疾病的风险更高综合症和心血管疾病。来自不同物种的令人信服的证据表明，母体肥胖会对后代的代谢健康产生负面影响，并影响各个系统；然而，有一项有限的研究调查肥胖母亲所生后代的心脏功能障碍。心肌病 20-40%的儿童发生与线粒体疾病相关的疾病，其中线粒体功能障碍更为常见肥胖儿童比正常体重儿童更常见。不幸的是，细胞和分子机制仍然知之甚少。这项研究的长期目标是确定终生影响和机制潜在的异常母体代谢环境对后代心脏代谢疾病的影响为通过母亲锻炼预防儿童肥胖的治疗策略提供证据。我们有最近建立了雌性小鼠孕前和妊娠期肥胖模型，其中雄性后代与雌性后代相比，葡萄糖不耐受和胰岛素抵抗的程度更大。为了解决性问题作为生物学变量，雄性和雌性后代都将用于：1）体内和体外评估无论是否运动，心脏对母亲肥胖的收缩特性； 2）确定肥胖母亲所生心脏的形态/结构改变和基因表达 without exercise; 3) 确定氧化应激和线粒体功能作为基础母亲肥胖和运动改变后代心脏代谢健康的机制。虽然运动对心脏功能的长期有益影响已在健康正常体重中得到充分证明据我们所知，我们的研究是第一项调查母亲运动作用的研究子代心脏功能的影响及其潜在机制强调性别差异线粒体功能。这项拟议研究的结果将增进我们对母亲如何运动可以改变心脏结构、线粒体功能和整体心脏功能；因此，可以为预防与儿童肥胖相关的心脏病提供新的干预措施。我们的建议很好与 NIH 减轻慢性病负担的使命相一致。