Project : USDA ARS

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Research Project: Nutritional Metabolism in Mothers, Infants, and Children

Location: Children's Nutrition Research Center

2018 Annual Report

Objectives
The overall goal of our research is to define the nutritional distresses and critical windows of development that alter physical activity (PA); understand the various factors that regulate mammary gland (MG) function in lactating mothers; and contribute to the development of nutritionally enhanced plant foods and assess their impact on human health. Specific objectives of this research include: 1) determine the effects of nutrition during critical window(s) of development on voluntary PA during late adolescence and middle age using mouse models; 2) determine the relative contributions of skeletal muscle mass, composition and contractile properties, exercise capacity, motor coordination, and behavior to the differences in voluntary PA induced by the nutritional perturbations incurred in early life; 3) determine the changes in gene and protein expression in skeletal and cardiac muscle and/or brain that contribute to the PA phenotypes induced by alterations in early life; 5) removed due to vacant position; 6) identify new genes required for calcium oxalate formation in Medicago truncatula; 7) identify genes required for calcium oxalate formation in Glycine max (soybean) and modify calcium oxalate content in Glycine max; 8) determine if microRNAs with plant-associated end chemistry can be functionally incorporated into a mammalian RNA-induced silencing complex/miRNA Ribonuclear Particle; 9) establish that food-associated microRNAs are present and functional in sera and tissues, and establish the relationship between dietary microRNA intake and metabolic changes; 10) determine the pathophysiology of lactation failure in obese women, including the role of progesterone, prolactin, and oxytocin in lactation in obese, as compared to normal weight women; 11) determine the importance of macrophage-mineralocorticoid receptor interaction to mammary gland development; 12) determine in obese and non-obese lactating women, the relationship between obesity, and maternal oxytocin response during lactation, and breastfeeding success; we will also test whether maternal oxytocin response is positively associated with mother-infant sensitivity and brain reward response to infant face and cry cues using functional magnetic resonance imaging; and 13) gain fundamental insights into the genetic foundations for variations in responses to dietary lycopene and to understand how lycopene may promote health and prevent chronic diseases.

Approach
These research studies will use various techniques to accomplish the research to be undertaken. Complex and coordinated studies will be performed in mouse models to define the nutritional perturbations (over- and under-nutrition) and critical windows of development (pre- vs. postnatal) that alter physical activity in adulthood; define the type of activity that is altered; and elucidate the physiological basis for the observed changes. Obese and non-obese recent mothers will be recruited, studied, and recorded to evaluate hormone responses to breastfeeding, particularly to evaluate prolactin secretion and progesterone levels as well as oxytocin response variables. MRI scans will be used to evaluate the activation of dopamine-associated brain reward regions in response to seeing own vs. unknown infant face cues. Additionally mice will be utilized to determine if ablation of macrophages during late pregnancy in obese mice will restore milk production and allow for the support of normal weight gain in cross-fostered litters; and we will attempt to understand how stem and progenitor cells are affected by obesity that lead to altered lactation capacity. Genome-wide association analysis will be employed to identify genomic loci associated with altered nutritional traits. We will also identify the plant genes that synthesize oxalate and calcium oxalate, and this information will be used to design strategies to manipulate oxalate content in important food plants (such as soybean) for the purpose of improving nutritional quality. Experiments will be conducted to determine whether food-associated plant microRNAs are present and functional in sera and tissues, and to establish the relationship between dietary microRNA intake and metabolic changes. Finally, studies will occur on enzyme kinetic assays and in vitro models of liver (HepG2) and prostate (DU-145) carotenoid absorption and metabolism to shed light on fundamental gene-lycopene interactions that underlay carotenoid bioactivity.

Progress Report
Significant research progress was accomplished during the year. To review the progress, please refer to project 3092-51000-056-01S (Project #1), 3092-51000-056-02S (Project #2), and 3092-51000-056-03S (Project #3).

Accomplishments
1. Impact of maternal diet on milk composition and milk microbiome. The impact of maternal diet on milk composition and the microbiota of the mother's milk are only partially known. Whether these factors, or the amount and type of complex milk sugars, are involved in the ability of mother's milk to protect her infant from disease is unknown. Researchers in Houston, Texas explored these factors in well-controlled human studies and found that not only does maternal diet affect the composition of the milk and the milk microbiome but that genetic factors regulating the type of complex sugars in milk do as well. The relationship among these findings and the passive immunity that has been demonstrated with breast feeding or human milk remain to be determined. This is important as identifying the factors that contribute or are responsible for the known passive immunity of breast milk would provide a framework to design dietary products and/or compounds which might boost the passive immunity in particularly vulnerable patient populations and provide sufficient precursors or process to optimize such passive immunity in otherwise healthy children.

2. Control of milk iron concentrations by genes. Iron deficiency in infants is a major problem world-wide. Researchers in Houston, Texas conducted a specific study (genome-wide association) using mice to understand how genetics regulates milk mineral concentrations. We found a region on chromosome 1 that increases milk iron by 35%. Our team demonstrated that transporter genes are also expressed at high levels in the mammary tissue of mice that carry genetic modifications to this region. This is important as the identification of these transporter genes could lead to strategies aimed at increasing the concentrations of iron in breast milk.

U.S. DEPARTMENT OF AGRICULTURE

Children's Nutrition Research Center: Houston, TX