Obesity

Question 1

Heritability

Answer 1

what percentage of variation in a trait on a population level can be attributed to genetic variation over environmental variation

Question 2

Heritability of obesity

Answer 2

• shift in average BMI from normal to overweight suggests it isn’t genetic
• but histogram changes shape as well
• must be some genetic influence as people are responding differently to the same environmental change

Question 3

POMC - MC1R

Answer 3

Melanogenesis
alpha»ACTH, beta, delta

Question 4

POMC breakdown

Answer 4

POMC - delta-MSH
- ACTH - alpha-MSH
- beta-MSH

Question 5

POMC - MC2R

Answer 5

steroidogenesis
ACTH

Question 6

POMC - MC3R

Answer 6

energy partitioning and homeostasis
delta>alpha, beta
inhibited by AgRP

Question 7

POMC - MC4R

Answer 7

energy partitioning and homeostasis
beta>alpha»>delta
inhibited by AgRP

Question 8

POMC - MC5R

Answer 8

sebum production
alpha»ACTH, beta, delta

Question 9

MC4Rs and obesity

Answer 9

• GsPCR
• children with mutation eat more
• adults with mutation choose food with higher fat content and lower sugar content
• alters preferences for food, as well as amount eaten
  -MC4R agonist therapy - approved for leptin deficiency, but not for obesity in the general population
• Mexican cave fish - little food so mutant keeps fish alive

Question 10

Leptin disorders

Answer 10

ob/ob mice = naturally occurring obese mice
- mutation in leptin gene

human congenital leptin deficiency
- normal birthweight
- hyperphagia after weaning
- increased fat mass
- no puberty
- impaired T cell immunity

Question 11

Leptin

Answer 11

• leptin promotes a starvation response to eat
• treat HCLD with leptin
• other forms of obesity cannot be treated with leptin as these people already have sufficient leptin!
• starvation responses suppress the immune and reproductive systems

Question 12

Agouti mice

Answer 12

agouti antagonises MC1R
- higher affinity than alpha-MSH
- so causes bleaching of coat

agouti antagonises MC4R
- in the brain
- causes obesity

characteristics
- age-onset metabolic defect
- hyperphagia
- increased adipocity
- hyperglycaemia
- hyperinsulinemia

Question 13

Labradors and feeding behaviour

Answer 13

• labradors have high feeding behaviour
• partial POMC deletion in 20% of pet labs
• but 95% have high feeding - why

Question 14

Leptin-melanocortin pathway

Answer 14

• leptin circulates in blood proportional to amount of body fat
• acts via LepR to POMC neurones in hypothalamus
• POMC releases melanocortin to alpha-MSH neurones in the paraventricular nucleus
• PVN = decreased food intake and increased metabolic rate