SummaryLymphocytes circulate through lymph nodes (LN) in search for antigen in what is believed to be a continuous process. Here, we show that lymphocyte migration through lymph nodes and lymph occurred in a non-continuous, circadian manner. Lymphocyte homing to lymph nodes peaked at night onset, with cells leaving the tissue during the day. This resulted in strong oscillations in lymphocyte cellularity in lymph nodes and efferent lymphatic fluid. Using lineage-specific genetic ablation of circadian clock function, we demonstrated this to be dependent on rhythmic expression of promigratory factors on lymphocytes. Dendritic cell numbers peaked in phase with lymphocytes, with diurnal oscillations being present in disease severity after immunization to induce experimental autoimmune encephalomyelitis (EAE). These rhythms were abolished by genetic disruption of T cell clocks, demonstrating a circadian regulation of lymphocyte migration through lymph nodes with time-of-day of immunization being critical for adaptive immune responses weeks later.

Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and ultimately, infant health outcomes. However, our understanding of whole body maternal and fetal metabolism during this critical life stage remains incomplete. The objective of this study is to utilize metabolomics to profile longitudinal patterns of fasting maternal metabolites among a cohort of non-diabetic, healthy pregnant women in order to advance our understanding of changes in protein and lipid concentrations across gestation, the biochemical pathways by which they are metabolized and to describe variation in maternal metabolites between ethnic groups. Among 160 pregnant women, amino acids, tricarboxylic acid (TCA) cycle intermediates, keto-bodies and non-esterified fatty acids were detected by liquid chromatography coupled with mass spectrometry, while polar lipids were detected through flow-injected mass spectrometry. The maternal plasma concentration of several essential and non-essential amino acids, long-chain polyunsaturated fatty acids, free carnitine, acetylcarnitine, phosphatidylcholines and sphingomyelins significantly decreased across pregnancy. Concentrations of several TCA intermediates increase as pregnancy progresses, as well as the keto-body β-hydroxybutyrate. Ratios of specific acylcarnitines used as indicators of metabolic pathways suggest a decreased beta-oxidation rate and increased carnitine palmitoyltransferase-1 enzyme activity with advancing gestation. Decreasing amino acid concentrations likely reflects placental uptake and tissue biosynthesis. The absence of any increase in plasma non-esterified fatty acids is unexpected in the catabolic phase of later pregnancy and may reflect enhanced placental fatty acid uptake and utilization for fetal tissue growth. While it appears that energy production through the TCA cycle increases as pregnancy progresses, decreasing patterns of free carnitine and acetylcarnitine as well as increased carnitine palmitoyltransferase-1 rate and β-hydroxybutyrate levels suggest a concomitant upregulation of ketogenesis to ensure sufficient energy supply in the fasting state. Several differences in metabolomic profiles between Hispanic and non-Hispanic women demonstrate phenotypic variations in prenatal metabolism which should be considered in future studies.

A possible discriminative effect of sphingomyelins, particularly those with two double bonds, and lysophosphatidylcholines was identified between subjects with normal weight and obesity independent of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol concentrations. Our results suggest weight status-dependent mechanisms for the development of IR with lysophosphatidylcholine C14:0 as a key metabolite in nonobese IR.

At The Power of Programming 2014 Conference, researchers from multiple disciplines presented and discussed the effects of early nutrition and other environmental cues during the first thousand days of life and beyond on the lifelong risk of noncommunicable diseases. This paper aims to summarize the concepts and some of the first achievements of the EarlyNutrition research project that initiated the conference.The EarlyNutrition consortium is a multinational, multidisciplinary research collaboration of researchers from Europe, the USA, and Australia. A focus is placed on exploration of the developmental origins of obesity, adiposity, and related health outcomes. Here we report on the first findings of experimental approaches, cohort studies, randomized clinical trials, and systematic reviews of current information, as well as position papers, which have all been developed with the involvement of project partners. We conclude that the EarlyNutrition project has successfully established itself during the first 2 project years as a very strong platform for collaborative research on early programming effects. The first results, available already at this early stage of the project, point to great opportunities for health prevention strategies via the implementation of dietary and lifestyle modifications, with large effect sizes. Further results are expected which should support improved recommendations and related policies for optimized nutrition and lifestyle choices before and during pregnancy, in infancy, and in early childhood.

view of the current status of the knowledge on metabolomics biomarkers for obesity, but further research is needed because the methods used in the studies to date are very homogenous, e.g. most used a targeted approach and therefore analyzed almost the same group of metabolites. Moreover, prospective studies are lacking since all of the studies are either case-control or cross-sectional studies.

33Background/Objectives: Elevated pre-pregnancy BMI (pBMI) and excess gestational weight gain (GWG) 34

The Power of Programming conference 2016 at Ludwig-Maximilians-Universität Munich brought together about 600 researchers and other stakeholders from around the world who reviewed the recent evidence on the lasting health impact of environment and nutrition during early life, from pre-pregnancy to early childhood. The conference was hosted by the Early Nutrition Project, a multidisciplinary research collaboration funded by the European Commission with collaborating researchers from 35 institutions in 15 countries in Europe, the United States and Australia. The project explores the early origins of obesity, adiposity and associated non-communicable diseases, underlying mechanisms and opportunities for prevention. The project also proactively supports translational application of research findings. In fact, some existing evidence has already been rapidly adopted into policy, regulatory standards and practice. Further, broad dissemination of findings is achieved through the established digital eLearning platform of the Early Nutrition eAcademy, video clip-based learning and graphically supported messaging to consumers. The project demonstrated powerful effects of early metabolic programming on later health. Compared to other common prevention strategies, modifying risk trajectories in early life can achieve a much larger risk reduction and be more cost-effective. While some effective prevention strategies have been promptly implemented in policy and guidelines, legislation and practice, in other areas, the uptake is limited by a paucity of quality human intervention trials and insufficient evaluation of the feasibility of implementation and econometric impact. This needs to be strengthened by future collaborative research work.

Background/Aims: Fetal metabolism may be changed by the exposure to maternal factors, and the route to obesity may already set in utero. Cord blood metabolites might predict growth patterns and later obesity. We aimed to characterize associations of cord blood with birth weight, postnatal weight gain, and BMI in adolescence. Methods: Over 700 cord blood samples were collected from infants participating in the German birth cohort study LISAplus. Glycerophospholipid fatty acids (GPL-FA), polar lipids, non-esterified fatty acids (NEFA), and amino acids were analyzed with a targeted, liquid chromatography-tandem mass spectrometry based metabolomics platform. Cord blood metabolites were related to growth factors by linear regression models adjusted for confounding variables. Results: Cord blood metabolites were highly associated with birth weight. Lysophosphatidylcholines C16:1, C18:1, C20:3, C18:2, C20:4, C14:0, C16:0, C18:3, GPL-FA C20:3n-9, and GPL-FA C22:5n-6 were positively related to birth weight, while higher cord blood concentrations of NEFA C22:6, NEFA C20:5, GPL-FA C18:3n-3, and PCe C38:0 were associated with lower birth weight. Postnatal weight gain and BMI z-scores in adolescents were not significantly associated with cord blood metabolites after adjustment for multiple testing. Conclusion: Potential long-term programming effects of the intrauterine environment and metabolism on later health cannot be predicted with profiling of the cord blood metabolome.