Genes and obesity

Question 1

what are estimates of heritability for BMI and WHR?

Answer 1

BMI- 40-70%

WHR- 30-60%

Question 2

what predicts obesity?

Answer 2

FH

• 2.5-4x more likely if one parent obese
• 10x more likely if both parents obese

Question 3

what are the main causes of early onset monogenic obesity?

Answer 3

mutations in 8 genes involved in leptin-melanocortin signalling pathway or neuronal differentiation of the PVN
Most found are involved in the appetite regulatory system in hypothalamus of brain
mongenic obesity is rare

Question 4

what is leptin?

Answer 4

protein hormone mainly expressed in & secreted from adipose tissue

Question 5

how does leptin signalling work?

Answer 5

gain weight–> more leptin secreted so increased signals to hypothalamus (where leptin receptors presents) –> reduced food intake & increased energy expenditure

Question 6

what information does leptin signalling transmit to brain?

Answer 6

short term- state of energy balance

long term- information about size of body fat depots

Question 7

what do leptin levels correlate to?

Answer 7

body fat content

Question 8

what are leptin levels like in most obese people?

Answer 8

high therefore associated with leptin insensitivity

-only 5-10% obese people have low leptin & they may benefit from leptin therapy

Question 9

summarise Thrifty gene hypothesis by neel?

Answer 9

• Humans would have selected for genes conferring efficient extraction & storage of nutrients and energy over thousands of yrs
• this theory now been disputed as according to it should all be fat in western society however in an obesogenic environment only 30-40% of people become overweight

Question 10

summarise Drifty hypothesis by Speakman?

Answer 10

• Instead of there being set point for body weight there is an upper intervention point and a lower intervention point
• We tightly regulate our body weight

Question 11

how has Drifty hypothesis evolved with time?

Answer 11

In last 50 years environment changed & those with higher upper intervention point have been predisposed to becoming fat; people with lower upper intervention point stay lean

Question 12

why is it important that there is an intervention point when fat/lean?

Answer 12

in order to keep body weight within limits and this is why we roughly stay same weight throughout life

Question 13

what gene/variant has the GWAS identified as being linked to reduced BMI?

Answer 13

val103lle variant of MC4R gene (causes 0.5kg reduction in BMI)
-one of the strongest currently known variants

Question 14

another example of a genetic variant associated w polygenic obesity?

Answer 14

FTO gene

Question 15

where are most variants located?

Answer 15

non-coding DNA

Question 16

in most individuals, genetic predisposition to obesity is what kind of basis?

Answer 16

polygenic

Question 17

what happens as number of risk alleles increases?

Answer 17

BMI increases

Question 18

comment on whether genetically predisposed people can modify their risk of developing obesity w exercise

Answer 18

genetic predisposition to obesity can be reduced by 40% by having active lifestyle

Question 19

to date, how many loci have been associated w polygenic obesity?

Answer 19

over 200