Endocrine control of food intake

Question 1

What decides whether you should be eating or not?

Answer 1

Hypothalalmus

Question 2

What is the key part of the hypothalamus involved in regulation of food intake?

Answer 2

Arcuate nucleus

Question 3

The arcuate nucleus is a circumventricular organ, what does this mean?

Answer 3

It has an incomplete blood-brain barrier so allows access to peripheral hormones

Question 4

What are the two neuronal populations in relation to food intake?

Answer 4

Stimulatory- NPY and Agrp neurones

Inhibitory- POMC neurones

Question 5

What do NPY and Agrp do to appetite?

Answer 5

Increase it

Question 6

Under normal conditions, what is POMC broken down into?

Answer 6

alpha-MSH

Question 7

What is alpha-MSH?

Answer 7

Endogenous agonist for MC4R which decreases food intake

Question 8

In relation to MC4R, what is Agrp?

Answer 8

Endogenous antagonist

Question 9

What happens when you need to eat?

Answer 9

You stimulate Agrp activity and block the inhibitory signal of alpha-MSH and stimulates food intake

Question 10

Of the three proteins, which one is there a known mutation of associated with appetite?

Answer 10

POMC deficiency

Question 11

What is POMC deficiency normally associated with?

Answer 11

Red hair and very pale skin

Question 12

What does leptin do?

Answer 12

Tells the brain how much fat there is in storage so regulates eating

Question 13

Where does leptin come from?

Answer 13

Fat

Question 14

What happens in people that are leptin deficient ?

Answer 14

They think that they are starving all the time because there isn’t any leptin to tell the brain that there are fat stores

Question 15

What would central or peripheral administration of leptin do?

Answer 15

Decrease food intake and increase thermogenesis- it activates POMC and inhibits NPY/Agrp

Question 16

What are leptin levels like in fat people?

Answer 16

High- It circulates in plasma in concentrations proportional to fat mass

Question 17

What happens with leptin in obese people?

Answer 17

They develop leptin resistance- ineffective as a weight control drug

Question 18

What are the effects of no leptin?

Answer 18

Hyperphagia, lowered energy expenditure and sterility

Question 19

What happens to children with no leptin?

Answer 19

They don’t go through puberty

Question 20

Why don’t children with leptin deficiency go through puberty?

Answer 20

The hypothalamus won’t be releasing GnRH because leptin has a permissive effect on its release

Question 21

Why do fat people have more insulin?

Answer 21

It circulates at levels proportional to body fat because fat people are more likely to be insulin resistant

Question 22

What is the body’s largest endocrine gland?

Answer 22

GI tract

Question 23

What is cholecystokinin involved in?

Answer 23

Gall bladder contraction
Gastrointestinal motility
Pancreatic exocrine secretion

Question 24

What is secretin involved in?

Answer 24

Pancreatic exocrine secretion

Question 25

What is GIP involved in?

Answer 25

Incretin activity

Question 26

What is ghrelin involved in?

Answer 26

Hunger | Growth hormone release

Question 27

What is gastrin involved in?

Answer 27

Acid secretion

Question 28

What is pancreatic polypeptide involved in?

Answer 28

Gastric motility | Satiation

Question 29

What is ghrelin released by?

Answer 29

Stomach

Question 30

How many amino acids long is ghrelin?

Answer 30

28

Question 31

What converts ghrelin to its active form?

Answer 31

Ghrelin O-acetyltransferase (GOAT)

Question 32

How do ghrelin levels change throughout the day?

Answer 32

It is high in the morning then goes down after breakfast and rises again until lunch (the pattern repeats for every meal)

Question 33

What effect does ghrelin have on appetite and how?

Answer 33

It increases appetite by directly modulating neurones in the arcuate nucleus: Stimulates Agrp/NPY neurones Inhibits POMC neurones

Question 34

What is both PYY and GLP-1 secreted by?

Answer 34

L-cells

Question 35

What shape are L cells?

Answer 35

Distinctive flask shape

Question 36

What is PYY 3-36?

Answer 36

Fullness hormone that is released post-prandially

Question 37

How does PYY 3-36 decrease appetite?

Answer 37

Directly modulates neurones in the arcuate nucleus: Inhibits NPY release Stimulates POMC neurones

Question 38

What is the incretin effect?

Answer 38

If you give someone oral glucose you get a much bigger insulin response than when you give same amount of glucose IV

Question 39

Why is there the incretin effect?

Answer 39

Glucose travelling in the GI tract stimulates the release of hormones that potentiate the effects of glucose-induced insulin release

Question 40

What is GLP-1?

Answer 40

Gut hormone coded for by preproglucagon gene that is released post prandially and has an incretin role and reduces food intake

Question 41

What are GLP-1 based drugs used to treat?

Answer 41

Diabetes mellitus

Question 42

Why does GLP-1 not cause hypoglycaemia?

Answer 42

It only stimulates glucose-induced insulin release so it only works when it is needed and when there is low glucose, there is no insulin release

Question 43

What is a problem with GLP-1?

Answer 43

It is quickly inactivated by DP-4 (dipeptidyl peptidase 4) so drugs have to be altered to have a longer half life

Question 44

What is saxenda?

Answer 44

Long acting GLP-1 agonist- structure of GLP-1 has been tweaked so it's more resistant to degradation, it also has a fatty acid group attached which stops it from being cleared from the circulation It has recently been approved as a treatment for obesity and diabetes

Question 45

What happens with high levels of PYY 3-36?

Answer 45

Nausea

Question 46

What comorbidities is obesity associated with?

Answer 46

``` Depression Stroke Sleep apnoea Myocardial infarction Hypertension Diabetes Bowel cancer Osteoarthritis Peripheral vascular disease Gout ```

Question 47

How much of body weight is due to heritability?

Answer 47

60-80%

Question 48

What is the thrifty gene hypothesis?

Answer 48

Specific genes were selected for to increase metabolic efficiency and fat storage, evolutionarily sensible to put on weight, thin people don't survive famine so don't pass on their genes- evolutionary drive to put on weight

Question 49

What is the adaptive drift hypothesis?

Answer 49

Used to be normal distribution of body weight: Thin people will not survive/be able to reproduce Fat people will be eaten Eventually, improved at defending against predators so excess bodyweight became a neutral change