Childhood infection and prevention of obesity

儿童感染与肥胖的预防

• 批准号: 8321437
• 负责人: Julie Parsonnet
• 金额: $ 73.48万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8321437
• 关键词: Acute; Address; Adolescence; Adult; Affect; Age; Appendicitis; Attention; Bacteriuria; Behavior; C-reactive protein; Cell Differentiation process; Centers for Disease Control and Prevention (U.S.); Cessation of life; Child; Childhood; China; Chronic; Chronic Disease; Cohort Studies; Communicable Diseases; Conceptions; Country; Cystic Fibrosis; Data; Desire for food; Development; Diarrhea; Differentiation and Growth; Disease; Documentation; Dysentery; Energy Intake; Energy Metabolism; Epidemic; Etiology; Expenditure; Family Sizes; Fatty acid glycerol esters; Fever; Food; Frequencies; Genetic; Glomerulonephritis; HIV; Habits; Health; Helicobacter Infections; Helicobacter pylori; Hepatitis C virus; Herpesviridae; Human; Hygiene; Incidence; India; Infant; Infection; Infection prevention; Infectious Agent; Inflammatory; Intake; Lead; Link; Lipolysis; Long-Term Effects; Longevity; Measures; Metabolic; Methods; Mexico; Microbe; Monitor; Morbid Obesity; Obesity; Otitis Media; Overweight; Parents; Pilot Projects; Play; Prevalence; Preventive; Principal Investigator; Randomized Clinical Trials; Recurrence; Reporting; Research; Rest; Rheumatic Fever; Scarlet Fever; Schistosomiasis; Series; Shapes; Signs and Symptoms; Societies; Streptococcal Infections; TNF gene; Teenagers; Temperature; Testing; Toxoplasmosis; Tuberculosis; Vaccines; Weight; Weight Gain; adipocyte differentiation; antimicrobial; cell growth; cytokine; diet and exercise; early childhood; ghrelin; improved; in utero; malignant stomach neoplasm; microbial; neonatal sepsis; neonate; novel vaccines; obesity in children; population health; premature; prenatal; programs; socioeconomics; trend

Program Director/Principal Investigator (Last, First, Middle): Parsonnet, Julie ABSTRACT Obesity is epidemic in the U.S. with almost 20% of children considered obese. The dramatic rise in overweight and obesity over the last 40 years coincides with equally dramatic decreases in childhood infections. Although these inverse trends-rising obesity and declining infection-could be only coincidentally related, we postulate that the relationship is, in fact, causal. Infectious agents are the most intimate and constant exposure in human existence. This fact is brought to our attention annually as each year, new infectious agents are unexpectedly identified as causal factors in chronic disease. With respect to obesity, infections can both increase energy expenditure and decrease appetite through a variety of direct and indirect mechanisms. Infection-induced cytokines can also affect adipocyte differentiation, growth and lipolysis. Since these are all critical factors in human weight gain, it is axiomatic-though currently quite controversial-to assume that infections may reduce weight in U.S. children. We hypothesize that frequent, chronic and/or severe prenatal and childhood infection prevent weight gain, overweight and obesity in children. Secondarily, we will address the hypothesis that early acquisition of specific chronic infections-e.g.,herpesviruses and H. pylori infection-protect against obesity. We plan to test these hypotheses in a series of pilot studies, followed by a longitudinal cohort study that follows young children from conception through at least 5 years and, ultimately to adolescence and adulthood, to determine how infectious diseases shape body habitus. Determination of infection in children will rely on two interrelated exposure measures: monitoring and reporting of daily symptoms and signs by parents, and documentation of seroconversion to a large panel of microbes. We will also explore mechanisms by which infection might alter weight gain including effects on resting energy expenditure, circulating inflammatory cytokines, and adipocytokine levels. The discovery of H. pylori in the 1980's demonstrated how accepted paradigms of disease causation can be astonishingly wrong. For obvious reasons, the study of obesity (like the study of stomach cancer before 1990) has focused on food. Although we are not revolutionary enough to say that food is immaterial to weight, we do propose that a significant proportion of the increase in weight in U.S. children over the last 40 years is related not to bad habits but to healthy, uninfected lives. This idea-if proved trued-would certainly prove transformative, potentially changing overall conceptions of weight, health and disease in childhood.

项目总监/首席研究员（最后，第一个，中间）：Parsonnet，Julie 抽象的 肥胖在美国流行，近20％的儿童被认为肥胖。在过去40年中，超重和肥胖的急剧上升与儿童感染的同样急剧下降。尽管这些反趋势增加的肥胖症和感染下降仅是偶然相关的，但我们假设这种关系实际上是因果关系。传染剂是人类生存中最亲密，最持续的暴露。这一事实每年都会引起我们的注意，因为每年，新的传染剂被意外地被确定为慢性疾病的因果因素。关于肥胖，感染既可以通过多种直接和间接机制来增加能量消耗，又可以减少食欲。 感染引起的细胞因子也会影响脂肪细胞分化，生长和脂解。由于这些都是人体体重增加的关​​键因素，所以它是公理的 - 尽管目前有争议的是，假设感染可能会减轻美国儿童的体重。 我们假设这种频繁，慢性和/或严重的产前和儿童感染可预防儿童体重增加，超重和肥胖。其次，我们将解决以下假设：早期获得特定的慢性感染-e.g。，疱疹病毒和幽门螺杆菌感染保护抗肥胖。我们计划在一系列的试点研究中检验这些假设，然后进行纵向队列研究，该研究跟随幼儿从受孕到至少5年，最终到青春期和成年，以确定感染性疾病如何塑造身体习惯。确定儿童感染将依赖两种相互关联的暴露措施：监测和报告父母的每日症状和迹象，以及将血清转化记录到大型微生物面板上。我们还将探讨感染可能改变的机制 体重增加，包括对静息能量消耗，循环炎性细胞因子和脂肪细胞因子水平的影响。 在1980年代发现幽门螺杆菌的发现表明，疾病因果关系的接受范式是如何惊人的。出于明显的原因，肥胖的研究（例如1990年之前的胃癌研究）集中在食物上。尽管我们没有足够的革命性，无法说食物与体重无关，但我们确实如此 建议在过去40年中，美国儿童体重增加的很大一部分与不良习惯有关，而与健康，未感染的生活有关。这个想法 - 如果被证明是奇特的，那么童年时体重，健康和疾病的总体概念肯定会变化。