L3 Obezity

Question 1

What is obesity and what is the main issue

Answer 1

Metabolic disorder leading to a positive energy ratio between energy intake v energy expenditure

If energy intake is sustained

Question 2

What are the major causes

Answer 2

Genetics
Epi genetics
Environment ie diet or activity

Question 3

How is bmi measured and what is obese

Answer 3

30kg/m-2

Question 4

How else is obesity measured

Answer 4

Fat percentage and waist circumference

Question 5

Why was it thought obesity could be evolutionary

Answer 5

Because some animals have adapted to store fat eg during hibernation or migration if birds

Question 6

Why is this discredited

Answer 6

70% of the western population isn’t obese even though food is plenty

Plus the disadvantages weigh out the advantages

Question 7

What was the first experiment linking genetics to obesity

Answer 7

Ob/of mouse with ob gene for leptin being mutant the mouse because obese with increased adiposity and reduced appetite control

Question 8

Which type of obesity is extremely rare and Mendelian (mutations)

Answer 8

Monogenic affecting appetite centre and satiety centre

Question 9

What does congenital leptin deficiency obesity mean

Answer 9

A type where you have a v rare leptin gene mutation = loss of leptin

(Treatment with leptin)

Question 10

Which other major types of mutations are there

Answer 10

Leptin receptor deficiency obesity

Pomc mutation

Mc4r mutations (most common) - loss of signalling to appetite control

Question 11

Which is autosomal recessive

Answer 11

Congenital leptin deficiency

Question 12

What does leptin deficiency cause

Answer 12

Extreme hunger and hyper insulin anemia leading to resistance

Question 13

Where are leptin receptor and pomc gene expressed

Answer 13

Arcuate nucleus in hypothalamus

Question 14

What is pomc

Answer 14

A precursor which is cleaved into hormones like acth, msh, b lipotropin

Question 15

Explain how leptin can cause satiety and increase energy expenditure

Answer 15

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

Question 16

Other than leptin what also stimulates pomc neurones

Answer 16

Insulin from b cells

Question 17

Which hormones block pomc signalling aswell as antagonise mc4r receptors

Answer 17

Npy and agrp

Question 18

What stimulates production of these/ gene exp increase

Answer 18

Ghrelin from the stomach

Question 19

Is there a snp which is protective from obesity which blocks agrp antagonising the mc4r receptor

Answer 19

Yes!

Question 20

Is polygenic obesity due to lack of leptin suually or leptin reisstance

Answer 20

Leptin resistance eg due to snp in lepr

Question 21

Candidate approach was used to study polygenic, why was monogenic used for this

Answer 21

Because they looked at genes in the hypothalamic pathway / melanocortin and leptin pathway

Question 22

What sort of genes had snps associated

Answer 22

Agrp, lepr, mc4r, npy and pomc

Question 23

What protein gene did Gwas see associated which isn’t in the hypothalamic path

Answer 23

FTO (fat mass obesity gene)

Question 24

What traits is fto associated with

Answer 24

Waist circumference and bmi (see fr)

Question 25

What protein is fto

Answer 25

Mrna de methylases eg works on leptin to de methylate- more leptin?

Question 26

Where is it expressed

Answer 26

Hypothalamus

Question 27

What else in fr seen it increase levels of if you have this certain snp (rs9939609)

Answer 27

Ghrelin via demethylation

Question 28

What genotype is this seen in (in further reading article)

Answer 28

AA genotype

Question 29

When is fto expression high

Answer 29

Feeding but stops during fasting as lack of leptin release

Question 30

If the odds ratio for fto is 1.6 what does this mean

Answer 30

The odds of you getting the disease is 1.6x more likely than baseline

Question 31

Give some examples of epi genetics affecting risk

Answer 31

Nutrition impacts methylation

Eg breastfeeding longer seen to reduce methylation of leptin gene but smoking during pregnancy increases it

Maternal obesity also linked to increased risk of offspring obesity

Question 32

How is microbiome incolved

Answer 32

Dysbiotic towards increased firmicutes

Also increased levels of scfa but unknown and it is controversial.

Question 33

How does leptin have effect on the orexigenic neurone with npy and agrp

Answer 33

Inhibits the neurone so stops agrp antagonistic effect

Question 34

What is sim1 mutation in monofenic obesity (fr)

Answer 34

Allows exp of more pvn neurones where mc4r are so if it’s mutated there are less