Biomarkers for fetal programming induced by late gestation malnutrition and for susceptibility to an early postnatal obesogenic diet of sheep

It is well established that adipose tissue development of sheep occurs at two different time windows of pregnancy; 1) during mid-gestation and, 2) in late gestation where maximum fat deposition occurred. Later, in adults, adipocytes (fat cells) will become the main site of lipid storage. Therefore, maternal diet as well as feed intake during postnatal life will have great impacts on this type of tissue. In the present study we will determine the effect of dietary correction of sheep exposed to an early postnatal high fat diet following late prenatal malnutrition (under vs. over) on the histology and genes regulating the pathway involved in the development, function and metabolism of different adipose tissue depots. RNA sequencing (RNA-seq) based on next generation sequencing (NGS) methods along with computational biology such as bioinformatics techniques (system biology) will be used to identify eQTLs, causal and regulatory gene networks, differentially expressed and co-expressed genes, hub genes and bio-markers for metabolic changes on adipose tissue and fat deposition via total RNA sequencing in sheep. Besides the above mentioned project we will also determine the epigenetic effect of ewes’ gestational nutrition on the genome and histological changes of newborn lambs umbilical cord from a Norwegian sheep experiment. The proposed project will addresses all of these goals from phenotypic observation and genetic characterization through systems biology to have in depth view of whole biological systems working as a unit, rather than investigating their individual components and understanding specific important pathways and pathway interactions involve with adipose tissues, lipid and glucose metabolism in sheep as well as epigenetic effect of maternal nutrition on the newborn lambs umbilical cord genome and histology.
1. To study the impact of dietary correction of adults’ sheep exposed to an early postnatal obesogenic diet following late gestation malnutrition on the histology of different type of adipose tissues.
2. To identify eQTLs, causal and regulatory gene networks, differentially expressed and co-expressed genes, hub genes and bio-markers of different types of adipose tissues of fetal programming (FP) for metabolic changes on adipose tissue and fat deposition via total RNA sequencing in sheep.
3. To examine whether maternal gestational malnutrition is reflected in:
a. histological modifications in the newborn lambs umbilical cord
b. epigenetic modifications in the newborn lambs umbilical cord genome which can be associated with the later modifications in adipose tissues development and function.