1. The Impact of Early Life Over- and Undernutrition on Fatty Acid Composition in Brain Lipids and their Association to Leptin-Related Gene Expression Christine Heerup - Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark, Hypothesis: Metabolic programming in early life causes changes in the brain lipid composition which might cause impaired leptin signalling. Nutrition-induced programming of the brain lipid compositionAppetite dysregulation 1

2. Experimental setup - Sheep study 3x2 factorial design feeding experiment Regular ON Ewes Offspring Early gestation (Week 0-15) Pre partum intervention Late gestation (Week 15-21) Lactation (0-3 days) Post partum intervention (Day 3-6 months) Re-establishment (6 months-2.5 years) Lambing Slaughtering UN HCHF Conv Norm n=6 n=7 n=4 n=6 Regular HCHF Conv Regular HCHF Conv Regular Membrane lipid derived fatty acids in Cortex mRNA expression of key genes involved in leptin signalling in hypothalamus 2 Christine Heerup - Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark, 50% of requirements 150% of requirements 100% of requirements

3. Results – Principal Component Analyses Impact of early life overfeeding on brain cortex fatty acid composition 3 Christine Heerup - Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark, Box: 25-75 Percentile Whiskers: Min-Max

4. Results – Correlation analyses Cortex fatty acids and Leptin signaling 4 Christine Heerup - Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark, Conclusion Post-partum overfeeding influences the cortex FA composition. Nutrition induced changes in the brain FA composition are detectable even into adulthood Pre-partum over- or underfeeding does not have any detectable effect on the cortex FA composition There is an association between percentages of certain FAs in cortex and expression of especially STAT3 in the hypothalamus

5. Thank you for listening! Lærke Johnsen – Department of Veterinary Clinical and Animal Science, University of Copenhagen, Frederiksberg, Denmark Mette Olaf Nielsen – Department of Veterinary Clinical and Animal Science, University of Copenhagen, Frederiksberg, Denmark Lars I. Hellgren – Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark Acknowledgements References http://www.thebabycorner.com/pregnancy-calendar/week-36/ http://keckmedicine.adam.com/content.aspx?productId=117&pid=1&gid=003272 http://medillsb.com/ArtistPortfolioLarge.aspx?IID=146889&AID=4962 5 Christine Heerup - Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark,