6. Control of appetite

Question 1

Where is the main appetite control centre located in the brain?

Answer 1

Arcuate nucleus within the hypothalamus

Question 2

What is the function of the arcuate nucleus?

Answer 2

Contains primary neurones that sense neuronal, nutrient and hormonal signals from the blood.

Primary neurones synapse with secondary neurones in other regions of the hypothalamus, which co-ordinate a response (altered feeding behaviour) via the vagus nerve.

Question 3

What are the 2 types of primary neurone in the arcuate nucleus?

Answer 3

1. Excitatory (orexigenic) neurones
   - stimulate appetite
   - via release of: neuropeptide Y and agouti-related peptide
2. Inhibitory (anorexigenic) neurones
   - suppress appetite
   - via release of pro-opiomelanocortin (POMC) - polypeptide prohormone enzymatically cleaved to produce several hormones inc. alpha-MSH - acts MC4 receptors.

Question 4

Why does a large meal produce feelings of euphoria and tiredness?

Answer 4

A reward system in the brain is also involved in control of feeding.

Stomach filled with food… anorexigenic release POMC… POMC enzymatically cleaved to produce a-MSH (satiety), but also beta-endorphin (euphoria and tiredness).

Question 5

Which hormones would be released by the body to stimulate or suppress appetite?

Answer 5

Stimulate appetite:
- ghrelin

Suppress appetite:

• PYY
• leptin
• insulin

Question 6

Describe the function of ghrelin.

Answer 6

• Peptide hormone released from stomach wall when empty (release inhibited by filling of stomach).
• Activates excitatory primary neurones in arcuate nucleus - stimulates appetite.

Question 7

Describe the function of PYY.

Answer 7

• Peptide hormone released by cells in the small intestine (ileum) and colon in response to feeding.
• Inhibits the excitatory neurones and activates the inhibitory neurones of the arctuate nucleus - suppresses appetite.

Question 8

Describe the PYY response following food intake in obese humans.

Answer 8

blunted

Question 9

Describe the function of leptin.

Answer 9

• Peptide hormone released into the blood by adipocytes in fat stores - feedback mechanism from fat stores.
• Inhibits the excitatory neurones and activates the inhibitory neurones of the arcuate nucleus - suppresses appetite.
• Induces expression of uncoupling proteins in mitochondria - production of heat rather than ATP.

Question 10

Describe the function of insulin in appetite regulation.

Answer 10

Secreted by beta cells of pancreatic Islets of Langerhans.

Suppresses appetite via similar mechanism to leptin (but less important than leptin in this role).

Question 11

Describe the function of amylin.

Answer 11

Secreted by beta cells of pancreatic Islets of Langerhans.

Roles not fully understood but known to suppress appetite, decrease glucagon secretion and slow gastric emptying.

Question 12

What is pramlintide?

Answer 12

Amylin analogue approved for treatment of Type 2 diabetes.

Question 13

What is congenital leptin deficiency and how is this treated?

Answer 13

• Loss of function mutation in leptin gene, causing obesity - very rare in humans.
• Patients treated with leptin injections.

Question 14

What is the effect of leptin injections in “common obesity” patients?

Answer 14

Little effect - “leptin resistance”