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