Valencik-Hunger Flashcards
What is anorexigenic?
suppresses appetite
What is orexigenic?
increases appetite
What is satiation? satiety?
satiation: cessation of hunger
satiety: sensation of being full
What are enteroendocrine cells?
endocrine cells of the GI tract & pancreas
What are incretins?
gut hormones that stimulate insulin secretion
What are oxyntic cells?
gastric parietal cells that release gastric acid
What are orexins? or aka hypocretins
NT that regulates arousal, wakefulness, hunger
Which 3 areas give peripheral signals to the hypothalamus and brainstem to control energy homeostasis?
adipose tissue
pancreas
GI tract
What are some long term signals related to hunger?
leptin-decreases hunger
insulin–decreases appetite
What are some short-term signals related to appetite?
ghrelin-increases hunger
tells you I’m full! With gastric emptying:
CCK
PYY
What’s the deal with leptin?
hormone that decreases hunger released in proportion to fat stores.
If you eat less & have less body fat–>less leptin will be produced.
Say you have a lot of leptin released….what are some mechanisms that counteract that?
minimizing energy usage
increasing appetite
The short term signals of the GI tract are released based off of which 2 things?
size of meals
number of meals
What are the different nuclei in the hypothalamus that are related to food intake?
Lateral nuclei (LN) Ventromedial nuclei (VMN) Paraventricular nuclei (PVN) Dorsomedial nuclei (DMN) Arcuate nuclei (ARC)
The laternal nuclei of the hypothalamus is the _______ center. The ventromedial nuclei of the hypothalamus is the _____ center.
LN: feeding center
VMN: satiety center
When you stimulate LN what do you get? When you destroy it–what happens?
lots of hunger–hyperphagia
destroyed–>no urge to eat (inanition), weight loss, muscle weakness, decreased metabolism
When you stimulate VMN what happens? When you destroy it?
Stimulate: aphagia, no urge to eat.
Destroyed: eat & become obese.
A lesion to the paraventricular nucleus leads to what?
excessive eating
A lesion to the dorsomedial nucleus leads to what?
less eating
What’s the deal with the arcuate nucleus?
multiple hormones are released from GI & adipose tissue & converge at AN to regulate eating.
So…it appears that which guys are on the anti-eating train?
PVN
VMN
Which guys are on the eating train?
LN
DMN
What are the 2 types of neurons found in the arcuate nuclei?
- anorexigenic
2. orexigenic
What do the anorexigenic neurons produce in the arcuate nucleus?
POMC/CART
CART–cocaine & amphetamine regulated transcript
**get alpha-MSH & CART peptide
What is produced by the orexigenic neurons in the arcuate nucleus?
AgRP/NPY
make agouti-related protein & neuropeptide Y
What are the gut hormones from the GI tract that affect the brain stem & hypothalamus in controlling hunger?
PP GLP-1 CCK PYY OXM Ghrelin
What are the adiposity signals that affect the hypothalamus & control hunger?
adiponectin
insulin
leptin
T/F the state of the nuclei in the hypothalamus affect secretion of the thyroid, pancreatic islet cells, adrenal gland.
True.
How does the arcuate nucleus in the hypothalamus receive info from the body?
mainly through the median eminence, lacks a BBB
receptors for a number of things, including insulin, GH, leptin & other peripheral signals.
Describe in basic terms how the arcuate nucleus neurons interact with the PVN to control hunger.
POMC/CART neuron in arcuate nucleus stimulates the neuron of the PVN causing decreased food intake & (via nucleus tractus solitarius) increased energy expenditure.
AGRP/NPY neuron in arcuate nucleus inhibits the neuron of PVN & POMC/CART causing increased food intake & decreased energy expenditure.
In more detail…how does POMC/CART neuron stimulate the neuron of the PVN to increase energy expenditure & decrease food intake?
POMC release alpha MSH which activates MCR3 & 4 on PVN.
CART peptide when released binds to unknown receptor on PVN.
What does inhibition of MCR4 play a role in? Excessive activation of MCR4?
MCR4 inhibition: obesity in children
MCR4 excessive activation: role in anorexia
Describe in more detail how AGRP/NPY inhibits PVN & POMC/CART to increase food intake.
AgRP is an antagonist of MCR4 (alphaMSH can’t affect PVN)
AgRP inhibits POMC via GABA release
NPY inhibits PVN & POMC/CART via Y1 receptors (hyperpolarization/inhibition).
What is excessive AgRP associated with?
obesity
What does NPY stimulate food intake of? What else does it do?
preferentially carbs
It reduces fatty acid oxidation, promotes carbohydrate oxidation and promotes fatty acid synthesis.
What does AgRP control in rodents?
coat color
Which family of hormones is NPY a member of? What are some of its family members?
pancreatic polypeptide family of hormones
other family members: pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY)
Where is NPY found? When does it increase?
arcuate nucleus
increases when you lose weight.
Where are orexins found? Where are their receptors found?
orexins–in the lateral & posterior hypothalamic areas.
have axonal projections throughout the brain
receptors throughout the CNS
What is the function of orexins?
increase eating
role in emotional & motivational aspects of feeding behavior
increase wakefulness
Where do anorexigenic responses mainly work? What are some examples of these?
hypothalamus
Glucagon-like peptide-1 (GLP-1) Cholecystokinin (CCK) Peptide tyrosine tyrosine (PYY) Pancreatic polypeptide (PP) Oxyntomodulin (OXM or OXY) Insulin-pancreas Leptin-fat
What are some examples of orexigenic hormones?
Ghrelin
Galanin (GAL)
Cortisol
What are the 2 main adipocyte hormones?
leptin
adiponectin
What does leptin do?
limits food intake
promotes synthesis of alpha-MSH (also anorexigenic)
reduces the effects of NPY at first
**leptin conc’n proportional to body fat (more w/ more fat)
How exactly does leptin control food intake?
leptin causes an increase in alphaMSH & CART, which bind to PVN. decrease in food intake.
leptin inhibits AGRP/NPY, limits ability of AGRP to antagonize MCR4 & limits NPY’s ability to bind Y1r. decrease in food intake.
Once again, what does alpha MSH bind to?
MCR4 receptor
How do you treat a leptin deficient patient?
subcu injections of recombinant leptin.
Note: most obese patients have a lot of leptin, but it doesn’t decrease their weight.
Is adiponectin anorexigenic or orexigenic?
depends
What is the function of adiponectin?
regulates basal metabolic rate
increases insulin sensitivity & fatty acid oxidation
What inhibits the activity of adiponectin? Levels are reduced in which people? increased in which people?
activity inhibited by adrenergic stimulation & glucocorticoids
high adiponectin levels in anorexic people & low levels in obese people.
What are some receptors for adiponectin & where are they found?
AdipoR1-muscle
AdipoR2-liver & brain (hippocampus & some hypothalamic nuclei)
What is the largest endocrine organ?
the GI tract
30 peptides expressed–>hormones, peptide NT, growth factors
T/F Gi tract mainly produces orexigenic hormones.
False. Mainly anorexigenic.
What are incretins?
Hormones that stimulate a decrease in blood glucose levels by increasing insulin secretion from the pancreas.
Ex: GLP-1 (glucagon-like peptide) & GIP (gastric inhibitory peptide OR glucose-dependent insulinotropic peptide)
What exactly does GLP-1 do?
Potentiates glucose-dependent insulin secretion
Inhibit glucagon secretion
Inhibit gastric acid secretion
Inhibit gastric emptying
Decrease appetite
also pancreatic beta cell proliferation & decreased apoptosis.
increases cardiac function & Cardioprotection
decreases endothelial dysfunction
Where is GIP expressed?
enteroendocrine K-cells of the duodenum & proximal jejunum
How does GIP begin? How is it inactivated?
pre-pro GIP
After cleavage–>GIP
inactivated by DPP-4 (dipeptidyl peptidase-4)
Which cells express genes for glucagon derived peptides?
L-cells of the small intestine
have a long prepropeptide to make glucagon
sequential processing is tissue specific
What is GRPP+Glucagon+IP-1?
Glicentin
What is Glucagon+IP1?
Oxintomodulin
What is GRPP+Glucagon?
proglucagon
What does GIP do?
increases lipogenesis
increase insulin secretion
What is oxyntomodulin?
Glucagon+IP-1
37 AA peptide derived from proglucagon
from enteroendocrine L cells of the distal gut
**incretin activity
When is oxyntomodulin secreted? Which receptor does it bind? What does it do?
secreted w/i 5-10 minutes of meal
binds GLP-1 receptor
**incretin activity
**suppresses gherkin effects in the brain
What happens when oxyntomodulin is injected subcu in obese patients?
suppresses appetite for 4 weeks.
Where is cholecystokinin expressed? How many forms?
expressed in duodenum & jejunum
also produced in the brain
4 forms–>CCK-33 most common
When does CCK increase? What is its half life?
increases w/i 15 minutes of eating
peaks @ 25 min
t1/2=1-2 minutes
What does CCK bind to?
GPCRs (CCK-1, CCK-2)
What happens when CCK binds to its receptors?
Gallbladder contracts
Pancreatic enzymes release
Gastric emptying is inhibited
**synergistic w/ leptin (reduces food intake)
What are the major members of the pancreatic polypeptide family?
pancreatic polypeptide
peptide tyrosine-tyrosine
NPY
Where is PP expressed? When does it increase?
expressed in distal GI
can’t cross BBB
increases 6 hours after meal
more secreted w/ higher caloric content of meal
When does PP increase aside from after a meal? What does it do?
w/ ghrelin, motilin, gastric distention, secretion of PP increases.
**action: decreases ghrelin expression.
What happens when you inject PP into healthy people?
decreases food intake by 25% w/i 24 hours.
Where is PYY produced/secreted?
enteroendocrine L-cells of ileum & colon
What leads to increased levels of PYY?
high fat–high PYY.
Which receptors does PYY bind?
Y1, but mainly Y2 receptor.
increases POMC & decreases NPY
What is the action of PYY?
Reduces ghrelin, gut motility, delays in gastric emptying, inhibits pancreatic bicarbonate and protein secretion and inhibits gallbladder contraction.
satiety effects via arcuate nuclei
What is ghrelin?
pre protein makes either it or obestatin, endogenous agonist of growth hormone, specifically GHS-R, stimulating release of GH
What is ghrelin secreted from?
stomach (gastric oxyntic cells), SI, colon
What is the structure of ghrelin?
28 AA protein w/ acyl side chain, n-octanoic acid (necessary to bind GHS-R)
What does ghrelin stimulate in the hypothalamus?
stimulates NPY/AgRP in arcuate nucleus
What is galanin? Where is it expressed?
29 AA peptide, orexigenic
expressed in gut & brain & binds GALR1 in hypothalamus
Insulin & leptin stimulate _____.
POMC/CART
Ghrelin activates ____.
AgRP/NPY
Leptin & PYY inhibit _____.
AgRP/NPY
The liver & GI can stimulate the vagus nerve–>NTS & cause____.
satiety, meal termination
