56.2 Control of Appetite Flashcards
What is the satiety centre?
Ventromedial hypothalamic nucleus
What is the hunger centre?
Lateral hypothalamic nuclei
Which hypothalamic nucleus is the integrative centre for peripheral signals of appetite?
Arcuate nucleus
What are the alimentary tract hormones involved in appetite?
Ghrelin, insulin
Where and when is Ghrelin produced?
*Specialised endocrine P/D1 cells in gastric mucosa of stomach
*The concentration increases before a meal and drops on eating.
Which neurons does ghrelin stimulate?
NPY/AgRP neurons
What is the function of ghrelin?
ghrelin is the only gastric hormone to increase appetite and decrease metabolism
How do the levels of leptin and insulin change throughout the day and in contrast with each other?
- 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)
Where is insulin released from and when?
Pancreatic beta cells
After a meal in response to increased plasma glucose
Which neurons do leptin and insulin stimulate and inhibit?
Stimulate POMC/CART neurons
Inhibit NPY/AgRP neurons
What kind of signal does insulin have on the hypothalamus?
Anorexigenic
What is CCK?
Cholecystokinin
How does CCK signal to the brain?
- Binds to receptors on vagal afferent nerves in submucosa
- Vagal afferent signals travel to the NTS in the dorsal vagal complex
What stimulates CCK release?
A meal
- due to introduction of HCl, amino acids, or fatty acids into duodenum
Where is cholecystokinin (CCK) released from?
I-cells of the duodenum (small intestine)
What is PYY?
Peptide tyrosin tyrosin
What kind of signal does PYY have on the hypothalamus/NTS?
Anorexigenic
Where does PYY bind?
Arcuate nucleus (POMC/CART) and NTS (nucleus of the solitary tract) in brainstem
Where is peptide tyrosin tyrosin (PYY) released from and when?
Ileum and colon (distal gut)
In response to food intake (mainly fat)
What is PP?
Pancreatic polypeptide
What kind of signal does PP have on the brain?
Anorexigenic
Where does PP bind to?
Arcuate nucleus (POMC/CART) and PVN
NTS in brainstem
May also act via vagus nerve
Where is pancreatic polypeptide (PP) released from and when?
Pancreatic PP cells in islets of Langerhans
In response to a meal, in proportion to caloric intake
What are the effects of GLP-1?
Inhibits gastric emptying, promotes satiety
What is GLP-1?
glucagon-like-peptide-1
Where does GLP-1 bind to?
Arcuate nucleus (POMC/CART)
NTS
Vagal afferents
Where is glucagon-like peptide 1 (GLP-1) released from and when?
L-cells of the intestines
After meal ingestion
What is Leptin?
peptide hormone that regulates food intake/ body mass/ reproductive function/ foetal growth/ proinflammatory immune response/ angiogenesis/ lipolysis.
What is the effect of Leptin on the arcuate nucleus?
Where is leptin synthesised and secreted from?
Synthesised + secreted by WAT fat cells
When lipid storage (body fat mass) increases
What kind of signal does leptin have on the hypothalamus?
Anorexigenic
What kind of signal does leptin have on the NTS?
Anorexigenic (satiety)
What can leptin and leptin receptor deficiency cause?
It is a rare cause of major obesity
What is congenital leptin deficiency associated with?
Congenital leptin deficiency is associated with severe early-onset obesity in humans
What is the role of leptin and when is it secreted?
- 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
What are the central signals?
Neuropeptide Y (NPY), alphaMelanocyte Stimulating Hormone (alphaMSH), mesolimbic reward system, social cues.
How do POMC/CART and NPY/AgRP neurons interact?
NPY/AgRP have an inhibitory effect on POMC/CART neurons through GABA release
How is the orbitofrontal cortex involved in food intake?
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
How is the VTA involved in food intake?
- 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
What are the downstream effects of stimulation of MC4Rs?
- Promotes satiety and decreases food intake via stimulation of lateral parabrachial nucleus
- Increases energy expenditure via activation of descending sympathetic pathways
What are the functions of the NPY/AgRP and POMC/CART neurons?
NPY/AgRP: orexogenic, signalling hunger
POMC/CART: anorexigenic, signalling satiety
What are the second-order neurons that POMC/CART and NPY/AgRP neurons project to called?
PVN satiety neurons/PVN anorexogenic centres
What are the two main opposing types of neurons in the arcuate nucleus?
NPY/AgRP
POMC/CART
What can abnormalities in rewarding eating behaviours lead to?
Eating disorders
Reward perverted towards low energy dense foods despite starvation, implicit ‘wanting’ of low cal foods
What does anorexigenic mean?
Reduces appetite
(/stimulates satiety)
What does destruction of the lateral nucleus lead to?
Anorexia
What does destruction of the ventromedial nucleus lead to?
Hyperphagia
What does orexigenic mean?
Stimulates appetite
(/inhibits satiety)
What is the mechanism of action of AgRP?
Inverse agonist at MC4Rs - inhibits the satiety response brought about by MC4R activation
What is the mechanism of action of GABA?
Inhibitory neurotransmitter at GABA-A and GABA-B
Allows NPY/AgRP neurons to inhibit POMC/CART neurons
Inhibits activation of lateral parabrachial nucleus
What is the mechanism of action of NPY?
Agonist at Y receptors
Potent orexigenic peptide - induces a robust feeding response
What is the role of the nucleus accumbens in food reward?
- 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
Where do neurons from the VTA project to?
Nucleus accumbens
Where do the POMC/CART and NPY/AgRP neurons in the arcuate nucleus project to?
Paraventricular nucleus (PVN)
Where is the hub of the mesolimbic reward system?
Ventral tegmental area (VTA)
Which hormone is chronically increased in Prader-Willi syndrome?
Ghrelin
Constant orexigenic signalling –> hyperphagia
Which neurotransmitter do POMC/CART neurons release?
α-melanocyte stimulating hormone (α-MSH)
Which neurotransmitters do NPY/AgRP neurons release?
- Neuropeptide NPY
- AgRP
- GABA
Which receptor does α-MSH bind to?
Melanocortin 4 (MC4) receptor
Which top-down factors can affect food intake?
Social cues, emotional cues, hedonistic behaviours
