Endo 14: Obesity ++ endocrine control of food intake

Question 1

Wha the function of arcuate nucleus ?

Answer 1

• involved in the regulation of food intake

–> integrates peripheral and central feeding signals

Question 2

What is meant by the fact that the arcuate nucleus is a circumventricular organ?

Answer 2

• means it has an incomplete BBB

- -> therefore allowing access to peripheral hormones

Question 3

What are the 2 types of neuronal populations in the arcuate nucleus?

Answer 3

a) STIMULATORY - inc app
- NPY + AGRP neurons

b) INHIBITORY - dec app
- POMC neurons

Question 4

in normal conditions, what happens in the melanocortin system?

Answer 4

• POMC = broken down to a-MSH
• -> which is an endogenous agonist of MC4R

–> so ur not hungry all the time

Question 5

When you need to eat you increase/ decrease Agrp activity

and block the inhibitory/stimulatory signal of a-MSH and stimulate food intake

Answer 5

When you need to eat you increase Agrp activity

and block the inhibitory signal of a-MSH and stimulate food intake

Question 6

POMC deficiency + MC4-R mutation causes:

Answer 6

POMC deficiency + MC4-R mutation causes: morbid obesity

Question 7

What is the function of leptin ?

Answer 7

• leptin = released from fat cells
• activates POMC + inhibits NYP/Agrp neurons
• -> tells brain how much fat is in storage
• -> therefore regulating eating

Question 8

What is a characteristic of leptin deficiency?

Answer 8

• patients with leptin deficiency will think they are starving all the time

Question 9

central / peripheral administration of leptin causes increase / decrease in food intake
and
increase / decrease in thermogenesis

Answer 9

central / peripheral administration of leptin causes decrease in food intake
and
increase in thermogenesis

Question 10

Why is leptin ineffective as a weight control drug?

Answer 10

• because most obese people = obese resistant
• -> they have leptin
• -> but doesn’t signal effectively

Question 11

in what situation may leptin administration be useful?

Answer 11

for those with leptin DEFICIENCY

Question 12

what might be the consequences of absence of leptin?

Answer 12

• hyperphagia
• lowered energy expenditure
• sterility

Question 13

What role does insulin have on food intake?

Answer 13

• circulating insulin levels = proportional to body fat
• there are insulin receptors in the hypothalamus
• insulin signals similarly to leptin

so central administration of insulin (directly into brain) –> reduces food intake

Question 14

What is ghrelin?

Answer 14

• hunger hormone
• released by stomach
• 28 a.acid long

Question 15

ghrelin is converted to its active form by the enzyme ________________

Answer 15

ghrelin is converted to its active form by the enzyme Ghrelin O- Acyltransferase (GOAT)

Question 16

note: levels of ghrelin drops after each meal then gradually increases until the next meal

Answer 16

-

Question 17

How does ghrelin increase appetite?

Answer 17

• directly modulates neurons in the arcuate nucleus
• STIMULATES Agrp/NPY neurons
• INHIBITS POMC neurons
• -> increases appetite

Question 18

What are PYY + GLP-1 secrete by?

Answer 18

• secreted by L cells in the distal s. intestine + colon

Question 19

How does PYY hormone work?

Answer 19

• PYY = released post-prandially
• directly modulates neurones in the arcuate nucleus
• it is a fullness hormone
• PYY decreases appetite
• -> inhibits NPY release
• -> stimulates POMC neurons

Question 20

How does GLP-1 hormone work?

Answer 20

• coded for by preproglucagon gene
• released post prandially (after eating)
• GLP1 = released after eating meal
• has incretin effect
• stimulates insulin secretion from the pancreas
  ( glucose induced insulin release )
• and reduces food intake

Question 21

How is GLP-1 degraded ?

Answer 21

• quickly inactivated by DP-4

Question 22

What is Saxenda?

Answer 22

• it is a long acting GLP-1 receptor agonist

- GLP-1 structure = modified –> so that it is more resistant to degradation

Question 23

How is the half life of saxenda prolonged?

Answer 23

• it has a fatty acid group attached –> which stops it from being cleared from the circulation

–> which gives it a much longer half life

Question 24

What are other uses of Saxenda ?

Answer 24

treatment for:

• diabetes
• obesity

Question 25

PYY as drug target

Answer 25

possible drug target for type 2 diabetes.

whereby drugs mimic GLP1

Question 26

What comorbitites are associated with obesity?

Answer 26

• depression
• sleep apnoea
• stroke
• bowel cancer
• osteoarthritis
• gout
• MI
• hypertension
• diabetes

Question 27

describe the thrifty gene hypothesis.

Answer 27

• thin people didn’t survive famines –> can’t pass on genes
• fat people / greedy people –> pass on genes
• -> suggests we have evolutionary drive to put on weight

Question 28

describe the drifty gene hypothesis.

Answer 28

• there used to be normal distribution of body weight
• too light: die/ not reproduce
• too heavy: gets eaten
• -> over time we got better at fending off predators –> so heavier people increase

Question 29

Where is MC4R located in?

Answer 29

in the paraventricular nucleus.

Question 30

The Ob gene is a recessive/ dominant mutation

what does it do?

Answer 30

recessive
–> codes for hormone leptin

note;

• presents profund obesity
• causes hyperplasia
• is diabetic
• decreases body temp

Question 31

Excessively high levels/ conc of PYY –> causes

Answer 31

nausea