Appetite Regulation

Question 1

Define ‘anorexigen’

Answer 1

Molecules which cause the inhibition of appetite e.g. by activating POMC or CART

Question 2

Define ‘orexigen’

Answer 2

Molecules which stimulate appetite e.g. by stimulating NPY, AgRP and MCH

Question 3

Which hypothalamic nucleus is involved in appetite regulation?

Answer 3

Arcuate nucleus

Question 4

Which neurone systems are involved in increasing appetite and decreasing energy expenditure when stimulated?

Answer 4

NPY and AgRP

Question 5

Which neurone systems are involved in decreasing appetite and increasing energy expenditure when stimulated?

Answer 5

POMC and CART

Question 6

Describe the neuropeptide Y (NPY) neurone system in the hypothalamus

Answer 6

These neurones express NPY and activation causes increased food intake and decreased energy expenditure

Question 7

Describe the agouti-related peptide hormone (AgRP) neurone system in the hypothalamus

Answer 7

AgRP is found on some of the neurones that present NPY also, and this peptide acts as a MC4R antagonist to inhibit appetite reduction

Question 8

What happens if an individual has a genetic deletion of the genes coding for the MC4R receptors?

Answer 8

The melanocortin molecules produced by the post-translational modification of POMC will be unable to bind to their MC4R target receptor, and therefore unable to exert its effects, and therefore appetite is not inhibited, leading to hyperplasia and subsequent obesity

Question 9

What happens if an individual has a genetic deletion of the genes coding for the MC4R receptors?

Answer 9

The melanocortin molecules produced by the post-translational modification of POMC will be unable to bind to their MC4R target receptor, and therefore unable to exert its effects, and therefore appetite is not inhibited, leading to hyperplasia and subsequent obesity

Question 10

How does insulin affect AgRP levels?

Answer 10

Insulin reduces the levels of AgRP as AgRP is involved in increasing appetite and reducing energy expenditure, which is counter-intuitive to the action of insulin.

Question 11

Name 7 anorexigenic molecules

Answer 11

Serotonin, PYY 3-36, POMC, GLP-1, CCK, leptin, elevated malonyl-CoA

Question 12

Explain how serotonin acts to decrease appetite and increase energy expenditure (anorexigen)

Answer 12

Serotonin production leads to serotonin binding to receptors in the arcuate nucleus of the hypothalamus:

At HTr2c serotonin binding increases POMC signalling to reduce appetite

At HTr1b serotonin causes decreased AgRP signalling to inhibit appetite increase

Question 13

Explain how PYY (3-36) acts to decrease appetite and increase energy expenditure (anorexigen)

Answer 13

PYY is secreted by the gut cells (enterocytes) in response to food and then travels in the blood to the hypothalamus where it inhibits the NPY neurones via the Y2 receptor, and stimulates the POMC neurones in order to decrease appetite and increase energy expenditure

Question 14

Explain how GLP-1 acts to decrease appetite and increase energy expenditure (anorexigen)

Answer 14

GLP-1 is secreted by L-intestinal cells in response to food, and thereafter it travels in the blood to the hypothalamus where it inhibits NPY and stimulates POMC

Question 15

Where is PYY produced?

Answer 15

Enterocytes (in response to food)

Question 16

Where is GLP-1 produced?

Answer 16

L cells in the intestine in response food

Question 17

Where is cholecystokinin (CCK) produced?

Answer 17

I type intestinal cells (enteroendocrine cells) in the duodenum and small intestine

Question 18

Explain how CCK acts to decrease appetite and increase energy expenditure (anorexigen)

Answer 18

CCK is secreted from I-type enteroendocrine cells in the duodenum and small intestine in response to food and it acts to suppress appetite via stimulation of the vagus nerve

Question 19

Explain how leptin acts to decrease appetite and increase energy expenditure (anorexigen)

Answer 19

High leptin levels cause AgRP levels to drop in order to inhibit appetite promotion

Question 20

Where is leptin produced?

Answer 20

Adipocytes, therefore if someone has more fat, they will secrete more leptin (which should reduce appetite)

Question 21

On which pathway does leptin primarily act?

Answer 21

AgRP; high leptin levels inhibit AgRP, low levels stimulate AgRP (to increase appetite)

Question 22

Name three orexigenic molecules/factors

Answer 22

Ghrelin, low leptin levels, low malonyl CoA

Question 23

Explain how ghrelin acts to increase appetite and decrease energy expenditure (anorexigen)

Answer 23

Ghrelin is secreted by the stomach in the absence of food, and binds to ghrelin receptors on NPY neurones and via the vagus nerve to increase appetite and decrease energy expenditure

Question 24

Explain how ghrelin acts to increase appetite and decrease energy expenditure (anorexigen)

Answer 24

Ghrelin is secreted by the stomach in the absence of food, and binds to ghrelin receptors on NPY neurones and via the vagus nerve to increase appetite and decrease energy expenditure

Question 25

Outline the role of malonyl CoA in decreasing appetite

Answer 25

Appetite is decreased where there is increase of LCFA CoA and malonyl-CoA as these molecules inhibit AgRP/NPY neurones and increased LCFA-CoA stimulates CART/POMC to decrease appetite

Question 26

Outline the role of malonyl-CoA in increasing appetite

Answer 26

A reduced malonyl CoA level increases AgRP/NPY activity and decreases POMC/CART pathways in order to increase appetite and decrease energy expenditure

Question 27

What causes an increase in malonyl-CoA levels?

Answer 27

There is glucose availability which leads to an increase in glycolysis which creates an elevated ATP:AMP ratio in the mitochondria which inactivates AMP-kinase (AMPK) which leads to the activation of ACC and inactivation of MCD (malonyl-CoA dehydrogenase) so more malonyl-CoA is formed and less is broken down.

Question 28

What causes a decrease in malonyl CoA levels?

Answer 28

There is a reduction in glucose availability which increases the AMP:ATP ratio in the mitochondria which leads to the activation of AMPK which activates MCD and inactivates ACC which leads to greater malonyl CoA breakdown and reduced synthesis, hence the reduced levels

Question 29

What drug may be given in order to increase appetite?

Answer 29

A form of cannabinoid; these act on CB1 receptors in the hypothalamus to increase appetite

Question 30

What drug may be given in order to decrease appetite?

Answer 30

- Amphetamine derivatives for 5HT (serotonin) and noradrenaline - SSRI derivatives, mostly 5HT - Cannibinoid antagonists - Leptin - GLP-1 agonists