Childhood infection and prevention of obesity

描述(申请人提供)：肥胖症在美国很流行，近20%的儿童被认为肥胖。在过去的40年里，超重和肥胖的急剧上升与儿童感染的急剧下降不谋而合。虽然这些相反的趋势--肥胖率上升和感染率下降--可能只是巧合地相关，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存在中最亲密、最持续的接触。这一事实每年都会引起我们的注意，因为每年都有新的感染源被意外地确定为慢性疾病的致病因素。关于肥胖，感染可通过各种直接和间接机制增加能量消耗和降低食欲。感染诱导的细胞因子也会影响脂肪细胞的分化、生长和脂肪分解。由于这些都是人类体重增加的关键因素，假设感染可能会减轻美国儿童的体重是不言而喻的--尽管目前很有争议。 我们假设，频繁、慢性和/或严重的产前和儿童感染可以防止儿童体重增加、超重和肥胖。其次，我们将解决这样的假设，即早期获得特定的慢性感染--例如疱疹病毒和幽门螺杆菌感染--可以预防肥胖。我们计划在一系列先导性研究中验证这些假设，随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身体习惯。儿童感染的确定将取决于两项相互关联的暴露措施：父母监测和报告日常症状和体征，以及向一大批微生物提供血清转换记录。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、循环炎性细胞因子和脂肪细胞因子水平的影响。 20世纪80年代S发现幽门螺杆菌表明，公认的疾病因果关系范式可能是令人震惊的错误。由于显而易见的原因，肥胖症的研究(就像1990年之前的胃癌研究)一直集中在食物上。尽管我们不够革命性地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不是与坏习惯有关，而是与健康、未受感染的生活有关。这个想法--如果被证明是真的--肯定会被证明是变革性的，可能会改变儿童时期对体重、健康和疾病的总体观念。

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.