Childhood infection and prevention of obesity

描述（由申请人提供）：肥胖在美国很流行，几乎20%的儿童被认为是肥胖。在过去40年里，超重和肥胖症的急剧增加与儿童感染的急剧减少相吻合。尽管这些相反的趋势肥胖率上升和感染率下降可能只是巧合，但我们假设这种关系实际上是因果关系。传染性病原体是人类生存中最亲密和持续的暴露。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致病因素。关于肥胖，感染可以通过各种直接和间接机制增加能量消耗并降低食欲。抑制诱导的细胞因子也可影响脂肪细胞分化、生长和脂解。由于这些都是人类体重增加的关键因素，因此假设感染可能会减轻美国儿童的体重是不言自明的，尽管目前相当有争议。 我们假设频繁、慢性和/或严重的产前和儿童期感染可预防儿童体重增加、超重和肥胖。其次，我们将讨论的假设，早期获得特定的慢性感染，疱疹病毒和H.幽门螺杆菌感染-预防肥胖。我们计划在一系列试点研究中测试这些假设，然后进行一项纵向队列研究，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体型。儿童感染的确定将依赖于两个相互关联的暴露措施：监测和报告父母的日常症状和体征，以及记录大量微生物的血清转化。我们还将探讨感染可能改变体重增加的机制，包括对静息能量消耗、循环炎性细胞因子和脂肪细胞因子水平的影响。 H. 20世纪80年代的幽门螺旋杆菌感染证明了公认的疾病因果关系的范式是多么的错误。出于显而易见的原因，肥胖的研究（如1990年之前的胃癌研究）一直集中在食物上。虽然我们还没有革命性地说食物对体重无关紧要，但我们确实提出，过去40年来美国儿童体重增加的很大一部分与不良习惯无关，而是与健康、未受感染的生活有关。这个想法如果被证明是正确的，肯定会被证明是变革性的，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.