Childhood infection and prevention of obesity

描述（由申请人提供）：肥胖在美国很流行，近20%的儿童被认为肥胖。在过去40年里，超重和肥胖人数急剧上升，与此同时，儿童感染人数也同样急剧下降。尽管这些相反的趋势——肥胖上升和感染下降——可能只是巧合相关，但我们假设这种关系实际上是因果关系。传染因子是人类存在中最亲密和最持续的接触。这一事实每年都引起我们的注意，因为每年都有新的传染性病原体被意外地确定为慢性疾病的病因。关于肥胖，感染可以通过各种直接和间接的机制增加能量消耗和降低食欲。感染诱导的细胞因子也可以影响脂肪细胞的分化、生长和脂肪分解。既然这些都是人类体重增加的关键因素，那么假设感染可以减轻美国儿童的体重是不言自明的，尽管目前还存在很大争议。我们假设频繁、慢性和/或严重的产前和儿童期感染可以预防儿童体重增加、超重和肥胖。其次，我们将讨论早期获得特定慢性感染的假设，例如：比如疱疹病毒和幽门螺杆菌感染——可以预防肥胖。我们计划在一系列试点研究中测试这些假设，然后进行纵向队列研究，跟踪幼儿从受孕到至少5年，最终到青春期和成年期，以确定传染病如何塑造身体习惯。确定儿童感染将依赖于两项相互关联的暴露措施：监测和报告父母的日常症状和体征，以及记录血清向一大组微生物转化的情况。我们还将探索感染可能改变体重增加的机制，包括对静息能量消耗、循环炎症细胞因子和脂肪细胞因子水平的影响。20世纪80年代幽门螺旋杆菌的发现表明，人们所接受的疾病成因范式可能是惊人的错误。由于显而易见的原因，对肥胖的研究（就像1990年之前对胃癌的研究一样）一直把重点放在食物上。虽然我们还没有革命到足以说食物对体重无关紧要，但我们确实提出，在过去40年里，美国儿童体重增加的很大一部分与坏习惯无关，而是与健康、未受感染的生活有关。这一观点——如果被证明是正确的——肯定会被证明是革命性的，可能会改变儿童时期对体重、健康和疾病的整体观念。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: There has been a 4-fold increase in obesity U.S. children over the last 40 years. Simultaneously, infections of childhood are disappearing due to changes in family size, improvements in hygiene, the addition of new vaccines, and other preventive health measures. This study intends to establish methods and collect preliminary data to determine whether decreases in childhood infection are linked to development of obesity.