Physiology: control of appetite

Question 1

What are the 5 hypothalamic nuclei involved in appetite regulation?

Answer 1

Arcuate nucleus
Ventromedial nucleus
Dorsomedial nucleus
Lateral nucleus
Paraventricular nucleus

Question 2

Of the dorsomedial nucleus, ventromedial nucleus, and lateral nucleus - which ones are involved in feeding (orexinergic) and which ones are involved in satiety (anorexinergic)?

Answer 2

Feeding: lateral nucleus
Satiety: dorso/ventromedial nuclei

Question 3

What are the 2 types of neurons in the arcuate nucleus?

Answer 3

POMC/CART neurons
AgRP/NPY neurons

Question 4

Of POMC/CART neurons and AgRP/NPY neurons - which group is responsible for feeding? Which is responsible for satiety?

Answer 4

Satiety: POMC/CART
Feeding: AgRP/NPY

Question 5

What does POMC stand for?

What substances do POMC/CART neurons release?

Answer 5

Pro-opiomelanocortin

a-MSH (alpha melanocyte stimulating hormone)
CART (cocaine and amphetamine related transcript)

Question 6

What are the 2 actions of a-MSH?

Answer 6

Acts on MCR-4 receptors on PVN neurons - to promote satiety.
Acts on MCR-3 receptors on AgRP/NPY neurons - to inhibit these, further promoting satiety.

Question 7

What substances do AgRP/NPY release?

Answer 7

AgRP (agouti related peptide)
Neuropeptide Y

Question 8

What is the function of AgRP?

Answer 8

Competitively antagonists MCR-4 receptors in PVN neurons, inhibiting actions of a-MSH - promoting feeding.

Question 9

What is the function of NPY?

Answer 9

Acts on Y1 receptors in the PVN to promote feeding.
Acts on Y1 receptors in POMC/CART neurons, inhibiting these, promoting feeding.

Question 10

What are the 2 actions of the paraventricular neurons?

Answer 10

Regulates food intake
Acts on the NTS to regulate sympathetic activity and energy expenditure

Question 11

What are the 3 short term hormones acting on the arcuate nuclei?
The 2 long term hormones acting on the arcuate nuclei?

Answer 11

Ghrelin, cholecystokinin, GLP-1
Leptin, insulin (think fat, diabetes)

Question 12

Ghrelin
- What is its signal?
- What releases it?
- Does it travel hormonally and/or neurally?
- What receptors does it bind to, and where, and its effect (activates/inhibits)?
- Does it promote feeding or satiety?

Answer 12

Hunger
Stomach cells
Hormonal (via bloodstream, crosses BBB by fenestrated capillaries in the median eminence); neural (by vagal afferents)
AgRP/NPY neurons
Promotes feeding.

Question 13

Cholecystokinin:
- What is its signal?
- What releases it?
- Does it travel hormonally and/or neurally?
- What receptors does it bind to, and where, and its effect (activates/inhibits)?
- Does it promote feeding or satiety

Answer 13

Fatty chyme entering duodenum
Duodenum
Neurally only - vagal afferents
AgRP/NPY (inhibits), POMC/CART (activates)
Promotes sateity

Question 14

GLP-1, leptin, insulin:
- What is its signal?
- What releases it?

Answer 14

GLP-1: presence of food in intestines, intestines secrete GLP-1.
Leptin: increased amount of adipocytes, adipocytes secrete leptin.
Insulin: increased BGLs, beta cells of pancreas release.

Question 15

GLP-1, leptin, insulin:
- Does it travel hormonally and/or neurally?
- Where are the receptors it binds to, and what is its effect (activates/inhibits)?
- Does it promote feeding or satiety

Answer 15

Hormonally
GLP-1, leptin, insulin receptors on AgRP/NPY (inhibits), POMC/CART (activates)
Promotes satiety.

Question 16

Role of the vagus nerve (independent of hormones) in regulating appetite
- What is its signal?
- How is the signal transported to the CNS?
- Effect?

Answer 16

GIT distension (espeically the stomach and duodenum) - due to food intake
Stretch inhibitory signals are sent mainly via that vagus nerve.
Promotes satiety.

Question 17

GLP-1 analogues: semaglutide
What are the 2 brands and
- Their dose
- Indication (T2DM vs weight loss)
- Amount of weight loss
- TGA approved?

Answer 17

Ozempic: lower dose, T2DM, some weight loss, yes (but shortage)
Wegovy: higher dose, weight loss, marked weight loss, no

Question 18

Ranitidine
- What receptor does it act on and its effect on this receptor? What is it’s main indication?
- What is a side effect?
- Why was it discontinued from the market?

Answer 18

Histamine receptor antagonist. Treats excess stomach acid.
Weight loss
Contaminated with NDMA - carcinogen

Question 19

What are 2 other metabolic drugs that promote weight gain?

Answer 19

Sulfonylureas and insulin
Steroids

Question 20

What are 4 types of brain/mental health drugs that promote weight gain?

Answer 20

Antidepressants (TCA’s, mirtazapine (histamine antagonists)
Antiepileptics
Antipsychotics
Cannabinoids