Obesity Mechanisms Flashcards
(7 cards)
1
Q
MC3R and obesity
A
- in the brain
- inactive = increased fat mass = decreased lean body mass
- loss of function mutation = delay in puberty onset
- plus decreased adult height, decreased lean mass, decreased IGF1 levels
- but no effect on BMI
- homozygous mutants = much delayed puberty (approx 20yo)
2
Q
Nutrient sensing
A
MC3R involved in:
- regulation of growth
- accrual of lean mass
- timing of sexual maturation
MC4R involved in:
- appetite regulation
- energy storage
brain responds to and translates circulating peripheral cues
3
Q
Feeding circuitry
A
- innervation from ARC to PVN, DMH and LH is delayed and decreased in ob/ob mice
- leptin reverses in developing mice, but not adult ob/ob
- leptin promotes neural outgrowth from ARC
- synapse number and activity onto POMC and NPY also altered in ob/ob
- leptin reverses and modulates synaptic plasticity
4
Q
Monogenic vs polygenic obesity
A
- GWAS = some genes affect where you store fat whilst others affect BMI/actual fat levels
- linear correlation between number of BMI risk alleles and mean BMI
Bassoon = protein with role in exocytosis of neurotransmitters
- binds piccolo
- protein truncating variants associated with increased severe obesity risk
- very rare so don’t know when onset occurs (adult-onset)
- is it at puberty? in freshers’ week when you have choice over food? mid-life?
5
Q
TrkB
A
- expressed in brain
- signalling implicated in axonal sprouting, dendritic growth, synapses and LTP
- central BDNF infusion in mice = decreased food intake and increased weight loss
- BDNF KO mice = obese
- TrkB hypomorph = severe obesity and increased linear growth
6
Q
Risk versus predictability
A
- difference between population risk scores and individual predictability
- genes predict but you can still choose how to use them!
7
Q
DESSERT
A
- once have had a big meal
- brain switches to crave high calorie foods
- to fit more calories in the small space left in stomach
- high sugar and fat food more desirable (i.e. DESSERT!)
