56.2 Control of Appetite

Question 1

What is the satiety centre?

Answer 1

Ventromedial hypothalamic nucleus

Question 2

What is the hunger centre?

Answer 2

Lateral hypothalamic nuclei

Question 3

Which hypothalamic nucleus is the integrative centre for peripheral signals of appetite?

Answer 3

Arcuate nucleus

Question 4

What are the alimentary tract hormones involved in appetite?

Answer 4

Ghrelin, insulin

Question 5

Where and when is Ghrelin produced?

Answer 5

*Specialised endocrine P/D1 cells in gastric mucosa of stomach
*The concentration increases before a meal and drops on eating.

Question 6

Which neurons does ghrelin stimulate?

Answer 6

NPY/AgRP neurons

Question 7

What is the function of ghrelin?

Answer 7

ghrelin is the only gastric hormone to increase appetite and decrease metabolism

Question 8

How do the levels of leptin and insulin change throughout the day and in contrast with each other?

Answer 8

• Leptin levels do not change much with meals or fasting (intermediate- to long-term signal)
• But insulin levels change dramatically in response to meals (short-term signal)

Question 9

Where is insulin released from and when?

Answer 9

Pancreatic beta cells
After a meal in response to increased plasma glucose

Question 10

Which neurons do leptin and insulin stimulate and inhibit?

Answer 10

Stimulate POMC/CART neurons
Inhibit NPY/AgRP neurons

Question 11

What kind of signal does insulin have on the hypothalamus?

Answer 11

Anorexigenic

Question 12

What is CCK?

Answer 12

Cholecystokinin

Question 13

How does CCK signal to the brain?

Answer 13

• Binds to receptors on vagal afferent nerves in submucosa
• Vagal afferent signals travel to the NTS in the dorsal vagal complex

Question 14

What stimulates CCK release?

Answer 14

A meal
- due to introduction of HCl, amino acids, or fatty acids into duodenum

Question 15

Where is cholecystokinin (CCK) released from?

Answer 15

I-cells of the duodenum (small intestine)

Question 16

What is PYY?

Answer 16

Peptide tyrosin tyrosin

Question 17

What kind of signal does PYY have on the hypothalamus/NTS?

Answer 17

Anorexigenic

Question 18

Where does PYY bind?

Answer 18

Arcuate nucleus (POMC/CART) and NTS (nucleus of the solitary tract) in brainstem

Question 19

Where is peptide tyrosin tyrosin (PYY) released from and when?

Answer 19

Ileum and colon (distal gut)
In response to food intake (mainly fat)

Question 20

What is PP?

Answer 20

Pancreatic polypeptide

Question 21

What kind of signal does PP have on the brain?

Answer 21

Anorexigenic

Question 22

Where does PP bind to?

Answer 22

Arcuate nucleus (POMC/CART) and PVN
NTS in brainstem
May also act via vagus nerve

Question 23

Where is pancreatic polypeptide (PP) released from and when?

Answer 23

Pancreatic PP cells in islets of Langerhans
In response to a meal, in proportion to caloric intake

Question 24

What are the effects of GLP-1?

Answer 24

Inhibits gastric emptying, promotes satiety

Question 25

What is GLP-1?

Answer 25

glucagon-like-peptide-1

Question 26

Where does GLP-1 bind to?

Answer 26

Arcuate nucleus (POMC/CART) NTS Vagal afferents

Question 27

Where is glucagon-like peptide 1 (GLP-1) released from and when?

Answer 27

L-cells of the intestines After meal ingestion

Question 28

What is Leptin?

Answer 28

peptide hormone that regulates food intake/ body mass/ reproductive function/ foetal growth/ proinflammatory immune response/ angiogenesis/ lipolysis.

Question 29

What is the effect of Leptin on the arcuate nucleus?

Answer 29

Question 30

Where is leptin synthesised and secreted from?

Answer 30

Synthesised + secreted by WAT fat cells When lipid storage (body fat mass) increases

Question 31

What kind of signal does leptin have on the hypothalamus?

Answer 31

Anorexigenic

Question 32

What kind of signal does leptin have on the NTS?

Answer 32

Anorexigenic (satiety)

Question 33

What can leptin and leptin receptor deficiency cause?

Answer 33

It is a rare cause of major obesity

Question 34

What is congenital leptin deficiency associated with?

Answer 34

Congenital leptin deficiency is associated with severe early-onset obesity in humans

Question 35

What is the role of leptin and when is it secreted?

Answer 35

* Leptin leads to decreased appetite * Leptin production increases exponentially with body fat mass, so it acts as direct feedback, maintaining weight within a narrow range * However, leptin levels can also be dissociated from this relationship by various events, such as starvation

Question 36

What are the central signals?

Answer 36

Neuropeptide Y (NPY), alphaMelanocyte Stimulating Hormone (alphaMSH), mesolimbic reward system, social cues.

Question 37

How do POMC/CART and NPY/AgRP neurons interact?

Answer 37

NPY/AgRP have an inhibitory effect on POMC/CART neurons through GABA release

Question 38

How is the orbitofrontal cortex involved in food intake?

Answer 38

Part of integrating sensory inputs to make decisions Combines info about taste, smell, visual inputs, texture Directs which foods to avoid and which to seek out

Question 39

How is the VTA involved in food intake?

Answer 39

- After eating, signals rewards - Leptin receptors activated (full) - decreases dopamine release, increases dopamine reuptake - Ghrelin receptors activated (hungry) - increases dopamine release Explains why food 'tastes better' when you are more hungry

Question 40

What are the downstream effects of stimulation of MC4Rs?

Answer 40

- Promotes satiety and decreases food intake via stimulation of lateral parabrachial nucleus - Increases energy expenditure via activation of descending sympathetic pathways

Question 41

What are the functions of the NPY/AgRP and POMC/CART neurons?

Answer 41

NPY/AgRP: orexogenic, signalling hunger POMC/CART: anorexigenic, signalling satiety

Question 42

What are the second-order neurons that POMC/CART and NPY/AgRP neurons project to called?

Answer 42

PVN satiety neurons/PVN anorexogenic centres

Question 43

What are the two main opposing types of neurons in the arcuate nucleus?

Answer 43

NPY/AgRP POMC/CART

Question 44

What can abnormalities in rewarding eating behaviours lead to?

Answer 44

Eating disorders Reward perverted towards low energy dense foods despite starvation, implicit 'wanting' of low cal foods

Question 45

What does anorexigenic mean?

Answer 45

Reduces appetite (/stimulates satiety)

Question 46

What does destruction of the lateral nucleus lead to?

Answer 46

Anorexia

Question 47

What does destruction of the ventromedial nucleus lead to?

Answer 47

Hyperphagia

Question 48

What does orexigenic mean?

Answer 48

Stimulates appetite (/inhibits satiety)

Question 49

What is the mechanism of action of AgRP?

Answer 49

Inverse agonist at MC4Rs - inhibits the satiety response brought about by MC4R activation

Question 50

What is the mechanism of action of GABA?

Answer 50

Inhibitory neurotransmitter at GABA-A and GABA-B Allows NPY/AgRP neurons to inhibit POMC/CART neurons Inhibits activation of lateral parabrachial nucleus

Question 51

What is the mechanism of action of NPY?

Answer 51

Agonist at Y receptors Potent orexigenic peptide - induces a robust feeding response

Question 52

What is the role of the nucleus accumbens in food reward?

Answer 52

- Gives feeling of pleasure/reward - Elicits neuronal activation for foods that were previously stimulatory: i.e. the reinforcing value of food - Links flavours paired with more calories with greater reward

Question 53

Where do neurons from the VTA project to?

Answer 53

Nucleus accumbens

Question 54

Where do the POMC/CART and NPY/AgRP neurons in the arcuate nucleus project to?

Answer 54

Paraventricular nucleus (PVN)

Question 55

Where is the hub of the mesolimbic reward system?

Answer 55

Ventral tegmental area (VTA)

Question 56

Which hormone is chronically increased in Prader-Willi syndrome?

Answer 56

Ghrelin Constant orexigenic signalling --> hyperphagia

Question 57

Which neurotransmitter do POMC/CART neurons release?

Answer 57

α-melanocyte stimulating hormone (α-MSH)

Question 58

Which neurotransmitters do NPY/AgRP neurons release?

Answer 58

- Neuropeptide NPY - AgRP - GABA

Question 59

Which receptor does α-MSH bind to?

Answer 59

Melanocortin 4 (MC4) receptor

Question 60

Which top-down factors can affect food intake?

Answer 60

Social cues, emotional cues, hedonistic behaviours