1. Are your genes to blame when your jeans don’t fit? Giles Yeo gshy2@cam.ac.uk @GilesYeo

2. Getting lunch – it’s a jungle out there Primal directives of life: 1.Find and eat food 2.Avoid becoming food 3.Reproduce 4.Repeat

3. Seven deadly sins

4. Energy balance Energy Intake Energy Expenditure Food Intake Basal Metabolism Physical Activity Adaptive Thermogenesis

5. Scully, Nature, 508(7496):S50-1, 2014

6. 0 2 4 6 8 10 12 14 1 BMI (kg/m 2 ) Changing pattern of obesity Frequency (%)

7. Twin studies Heritability of BODY WEIGHT = Heritability of HEIGHT

8. Zhang et al (1994). NATURE 372: 425-432 The discovery of leptin

9. Yeo and Heisler, 2012 Brain control of food intake Genetic modifiers Hormonal and nutritional cues Brain response and translation

10. Disruption of melanocortin signalling causes severe obesity Mutation resulting in obese human Mutation resulting in obese mouse

11. Human congenital leptin deficiency normal birthweight hyperphagia after weaning no food preference no defect in BMR or energy expenditure increased fat mass (57%) normal height do not undergo puberty impaired immune function

12. 3yr old weighing 42kg7yr old weighing 32kg Human congenital leptin deficiency Daily leptin treatment

14. Monogenic vs Polygenic Obesity

15. Loos, Best Prac& Res Clin Endo & Met, 2009 GWAS and common obesity

16. Willer et al, Nature Genetics, 2009

17. Locke et al, Nature 2015

18. Risk vs diagnosis

19. Your genes are like a hand of poker You can’t do anything about the cards you have But you can choose how to play them

20. There’s always time and (tummy) space for dessert

21. Are we all sinners?

22. Dr Giles Yeo gshy2@cam.ac.uk @GilesYeo