Maternal stress and obesity alter milk immunobiology and impair infant growth

母亲压力和肥胖会改变乳汁免疫生物学并损害婴儿生长

• 批准号: 8684689
• 负责人: Kelly F Ethun
• 金额: $ 26.78万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8684689
• 关键词: Acute; Address; Adverse effects; Affect; Age-Months; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Attenuated; Behavior assessment; Birth; Body Weight; Body mass index; Breast Feeding; Care given by nurses; Chronic; Chronic stress; Data; Development; Diet; Discipline of Nursing; Eating; Emotional; Environment; Exposure to; Fatty acid glycerol esters; Female; Fostering; Glucocorticoids; Growth; Growth Factor; Health; Hormonal; Housing; Human; Human Milk; Hydrocortisone; Immune; Immunity; Immunobiology; Immunoglobulins; Infant; Infant Development; Infant Health; Infection; Inflammatory; Insulin-Like Growth Factor I; Interleukin-6; Intervention; Lactation; Lead; Leptin; Long-Term Effects; Macaca mulatta; Measures; Mediating; Metabolic; Milk; Milk Substitutes; Mission; Modeling; Monitor; Mothers; National Institute of Child Health and Human Development; Newborn Infant; Obesity; Pattern; Phenotype; Postpartum Period; Postpartum Women; Production; Prospective Studies; Resistance; Risk; Role; Secretory Immunoglobulin A; Serum; Signal Transduction; Somatomedins; Stress; TNF gene; Testing; Translating; Visceral; Weaning; Weight; Woman; adipokines; adiponectin; cytokine; feeding; human data; improved; inflammatory marker; maternal stress; public health relevance; social; social stress; stressor

DESCRIPTION (provided by applicant): Evidence from human and animal studies show that chronic stress exposure and obesity synergize to elevate circulating stress and pro-inflammatory signals. What is less clear and particularly important for nursing mothers, however, is whether these signals translate to milk and affect infant development. Human milk contains many hormonal and immunological signals including cytokines, adipokines, immunoglobulins (Ig), and growth factors that mediate infant health and development; however, it is not known whether and to what extent maternal stress and obesity may alter these and produce adverse growth trajectories for infants. Because stressor exposure and diet are difficult to manipulate in postpartum women, social subordination in group-housed rhesus macaques represents a translational model to assess how maternal factors may affect milk immunobiology and negatively impact infant growth and health. To disentangle prepartum maternal stress from postpartum stress, fifty-six newborns will be cross-fostered to mothers of the same or different ranks. In addition, half of the mother-infant dyads will be maintained on a low calorie diet through lactation while the other half will be switched to a rich dietary condition. Behavioral assessments of maternal care, nursing patterns, and social rank will be obtained throughout lactation. Food intake in the mothers and infants during weaning will be monitored through automated feeders. Aim 1 will test the hypothesis that chronic social stress and adiposity will synergize to increase stress and inflammatory signals in milk. This aim will be accomplished by measuring cortisol, cytokine and adipokine markers in milk and serum from lactating rhesus monkeys of different social rank (dominant vs. subordinate) and postpartum diet exposure (high calorie vs. low calorie). Aim 2 tests the hypothesis that chronic social stress and adiposity will interact to decrease immune defense components in milk. Milk levels of sIgA in lactating dams will be evaluated in parallel with stress and inflammatory markers studied in Aim 1. Finally, Aim 3 will determine the contribution of milk signals studied in aims 1 and 2 to infant growth and health trajectories. Specifically, it will test the hypothesis that pro-inflammatory cytokines and adipokines significantly predict infant growth in addition to milk energy in a rich dietary environment. Taken together, findings from this study will better define how milk signals induced by maternal stress and obesity may affect infant growth and health, consistent with the mission of NICHD. Furthermore, findings from this study will lead to prospective studies to determine what interventions alleviate these adverse effects of maternal stress and obesity on infant health.

描述（由申请人提供）：人类和动物研究的证据表明，慢性应激暴露和肥胖协同以提高循环压力和促炎信号。但是，对于护理母亲而言，不太清楚，尤其重要，是这些信号是否转化为牛奶并影响婴儿的发育。人乳包含许多激素和免疫信号，包括细胞因子，脂肪因子，免疫球蛋白（IG）以及介导婴儿健康和发育的生长因子；但是，尚不清楚孕产妇的压力和肥胖症是否会改变它们并在多大程度上改变婴儿的不良生长轨迹。因为在产后妇女中很难操纵压力源的暴露和饮食，因此群体猕猴的社会服从代表了一种转化模型，以评估产妇因素如何影响牛奶免疫生物学并对婴儿的生长和健康产生负面影响。为了将产前孕产妇应力与产后压力解散，将五十六名新生儿交叉派往相同或不同等级的母亲。此外，一半的母子二元组将通过哺乳期低卡路里的二元组，而另一半将转变为富含饮食的状况。在哺乳过程中将获得对孕产妇护理，护理模式和社会等级的行为评估。断奶过程中母亲和婴儿的食物摄入量将通过自动喂食器进行监测。 AIM 1将检验以下假设：慢性社会压力和肥胖将协同增强牛奶中的压力和炎症信号。该目标将通过测量牛奶中的皮质醇，细胞因子和脂肪因子标记，以及来自不同社会等级（主要的下属）和产后饮食暴露（高热量与低热量）的泌乳恒河猴的血清。 AIM 2检验了以下假设：慢性社会压力和肥胖将相互作用以减少牛奶中的免疫防御成分。哺乳水坝中SIGA的牛奶水平将与AIM 1中研究的压力和炎症标记并行评估。最后，AIM 3将确定AIMS 1和2中研究的牛奶信号对婴儿生长和健康轨迹的贡献。具体而言，它将检验以下假设：促炎性细胞因子和脂肪因子和脂肪因子在丰富的饮食环境中除牛奶能量外，还可以显着预测婴儿的生长。综上所述，这项研究的发现将更好地定义孕产妇压力和肥胖引起的牛奶信号如何影响婴儿的生长和健康，这与NICHD的任务一致。此外，这项研究的发现将导致前瞻性研究，以确定哪些干预措施减轻了孕产妇压力和肥胖对婴儿健康的不利影响。