are your genes to blame when your jeans don’t fit? giles yeo [email protected] @gilesyeo
TRANSCRIPT
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Getting lunch – it’s a jungle out there
Primal directives of life:
1. Find and eat food2. Avoid becoming food3. Reproduce4. Repeat
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Seven deadly sins
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Energy balance
EnergyIntake
EnergyExpenditure
Food IntakeBasal MetabolismPhysical Activity
Adaptive Thermogenesis
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Scully, Nature, 508(7496):S50-1, 2014
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BMI (kg/m2)
Changing pattern of obesityFrequency (%)
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Twin studies
Heritability of BODY WEIGHT = Heritability of HEIGHT
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Zhang et al (1994). NATURE 372: 425-432
The discovery of leptin
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Yeo and Heisler, 2012
Brain control of food intake
Genetic modifiers
Hormonal and nutritional cues
Brain response and translation
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Disruption of melanocortin signalling causes severe obesity
Mutation resulting in obese human
Mutation resulting in obese mouse
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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
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3yr old weighing 42kg 7yr old weighing 32kg
Human congenital leptin deficiency Daily leptin treatment
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Monogenic vs PolygenicObesity
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Loos, Best Prac& Res Clin Endo & Met, 2009
GWAS and common obesity
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Willer et al, Nature Genetics, 2009
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Locke et al, Nature 2015
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Risk vs diagnosis
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Your genes are like a hand of poker
You can’t do anything about the cards you haveBut you can choose how to play them
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There’s always time and (tummy) space for dessert
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Are we all sinners?
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Dr Giles Yeo [email protected]@GilesYeo