L3 Obezity Flashcards
What is obesity and what is the main issue
Metabolic disorder leading to a positive energy ratio between energy intake v energy expenditure
If energy intake is sustained
What are the major causes
Genetics
Epi genetics
Environment ie diet or activity
How is bmi measured and what is obese
30kg/m-2
How else is obesity measured
Fat percentage and waist circumference
Why was it thought obesity could be evolutionary
Because some animals have adapted to store fat eg during hibernation or migration if birds
Why is this discredited
70% of the western population isn’t obese even though food is plenty
Plus the disadvantages weigh out the advantages
What was the first experiment linking genetics to obesity
Ob/of mouse with ob gene for leptin being mutant the mouse because obese with increased adiposity and reduced appetite control
Which type of obesity is extremely rare and Mendelian (mutations)
Monogenic affecting appetite centre and satiety centre
What does congenital leptin deficiency obesity mean
A type where you have a v rare leptin gene mutation = loss of leptin
(Treatment with leptin)
Which other major types of mutations are there
Leptin receptor deficiency obesity
Pomc mutation
Mc4r mutations (most common) - loss of signalling to appetite control
Which is autosomal recessive
Congenital leptin deficiency
What does leptin deficiency cause
Extreme hunger and hyper insulin anemia leading to resistance
Where are leptin receptor and pomc gene expressed
Arcuate nucleus in hypothalamus
What is pomc
A precursor which is cleaved into hormones like acth, msh, b lipotropin
Explain how leptin can cause satiety and increase energy expenditure
Binds to lepr on arcuate nucleus which then expresses more pomc which then is cleaved into msh etc
A- msh then binds to mc4r activating it and this causes satiety signals
Other than leptin what also stimulates pomc neurones
Insulin from b cells
Which hormones block pomc signalling aswell as antagonise mc4r receptors
Npy and agrp
What stimulates production of these/ gene exp increase
Ghrelin from the stomach
Is there a snp which is protective from obesity which blocks agrp antagonising the mc4r receptor
Yes!
Is polygenic obesity due to lack of leptin suually or leptin reisstance
Leptin resistance eg due to snp in lepr
Candidate approach was used to study polygenic, why was monogenic used for this
Because they looked at genes in the hypothalamic pathway / melanocortin and leptin pathway
What sort of genes had snps associated
Agrp, lepr, mc4r, npy and pomc
What protein gene did Gwas see associated which isn’t in the hypothalamic path
FTO (fat mass obesity gene)
What traits is fto associated with
Waist circumference and bmi (see fr)
