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Metabolic regulation of growth and body composition: key modulators of long-term health

Final Report Summary - META-GROWTH (Metabolic regulation of growth and body composition: key modulators of long-term health)

The burden of modifiable non-communicable diseases such as obesity, diabetes, heart disease and certain forms cancer has markedly increased for the European population, with a large impact on the quality of life of people and the related costs to society. Increasing evidence points to a major contribution of developmental origins of the lifelong risk of non-communicable diseases through environmental and particularly nutritional influencing factors acting during the period the time period of developmental plasticity in about the first 1000 days of life, i.e. during pregnancy and the first two years of life. The potential for reducing lifelong disease risk the first 1000 days of life is enormous. Understanding underlying mechanisms of early life programming of long-term health can improve. The META-GROWTH explored metabolic and epigenetic mechanisms of the regulation of pre- and postnatal growth patterns, which are strong predictors of lifelong health. We established state of the art methods for assessing genomewide epigenetic modification of gene expression and novel and powerful methodology for precise quantification of numerous substances in minute amounts body fluids, using high troughput methodology capable of analysing thousands of samples (targeted metabolomics with liquid chromatography triple mass spectrometry). In addition, we established complex methodology for the management and analysis of huge datasets created by the application of these methods to numerous and often very large cohort and intervention studies, covering critical time periods of developmental programming from pregnancy through infancy and childhood up to young adulthood. Although the chosen approach was rather ambitous and implied considerable risks, the project was highly successful and achieved enormous scientific and technological progress, extending knowledge far beyond established knowledge. We determined eraly growth characteristics that predict later disease development. We also identified metabolic signals that predict increased weight gain both pre- and postnatally as well as later overweight and obesity, adiposity, insulin resistance and the metabolic syndrome. We described marked sex and gender differences in metabolomic regulation both in young adults and in newborn infants. Epigenetic markers for exposure to prenatal tobacco smoking and for bodyfat ness in young children were characterised and offer new oppoprtunities for the mechanistic understanding of related developmental programming effects. Novel biomarkers were identified that are highly promising candidates for practical application in research studies and in practical application. In addition to the work planned at the start of the project, considerable further work was added exploring novel concepts and hypotheses, which created considerable added value over and above the plans laid down in the grant applicatrion. The high level of scientific productivity is documented by a large number of up to now 115 scientific publications reporting work supported by this ERC grant. The established, cutting edge methodologies, the hugely increased knowledge and experience, and the refined concepts and the novel hypotheses developed will enable us to continue and expand the work after the end of the project lifetime. In addition to markedly advancing scientific knowledge, we also achieved a high level of capacity building among younger researchers and established close and highly productive international collaborations. Transfer of knowledge and technology for translational application has already occurred to a large extent with application in guidelines on maternal and infant nutrition, regulatory standards on infant feeding, press and other media reports, broad outreach through digital distance learning initiatives of our group that are supporte i.a. by two European Eramus + Capacity Building in Higher Education grants, and research collaborations aiming at the development and evaluation of improved products for infant feeding. The accumulated advanced scientific knowledge and methodological strengths build a solid foundation for continued high level research, already supported by further European and national grants. Overall, the project funding provided by the ERC has enabled highly successful scientific work and transfer of knowledge into application to support the health and well being of people, and we are extremely grateful for the opportunities provided by the ERC Adavanced Grant.