Are your genes to blame when your jeans don’t fit?

Giles Yeogshy2@cam.ac.uk

@GilesYeo

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

0

2

4

6

8

10

12

14

1 13 16 19 22 25 28 31 34 37 40 43 46 49

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 gshy2@cam.ac.uk@GilesYeo