Valencik: Satiety Lecture Flashcards
suppress appetite
anorexigenic
increase appetite
orexigenic
satiation vs satiety
cessation of hunger vs sensation of being full
Gut hormones that stimulate insulin secretion
incretins
Gastric parietal cells that release gastric acid
oxyntic cells
What are two long-term signals for hunger/satiety?
leptin & insulin
Long term signal Secreted in proportion to fat stores. Eat less, less body fat, less of this signal is produced However, body adapts by: Minimizing energy usage Increasing appetite
leptin
Long term signal
Decreases appetite
insulin
Factors involved in short-term signaling of hunger/satiety
GI tract hormones - modulated by size/number of meals
Ghrelin - makes you hungry
CCK, PYY - make you full
5 neural centers that regulate food intake
lateral nuclei ventromedial nuclei (VMN) paraventricular nuclei (PVN) dorsomedial nuclei (DMN) arcuate nuclei (ARC)
The feeding center
When stimulated, hunger increases a lot
When destroyed, there is no urge to eat
lateral nuclei
The satiety center
When stimulated, there is no urge or a refusal to eat
When destroyed, you have a crazy appetite & may continue to eat until you are obese
ventromedial nuclei
Lesions in this nucleus lead to excessive eating
paraventricular nuclei
Lesions in this nuclei depress eating
dorsomedial nuclei
Site where multiple hormones released from the GI & adipose tissue converge to regulate eating & energy consumption
arcuate nuclei
Two types of neurons found in the arcuate nuclei
anorexigenic –> POMC/CART
orexigenic –> AgRP/NYP
What happens when you stimulate POMC/CART neurons?
production of alpha MSH which binds to MCR-3/4 & decreases food intake & increases sympathetic activity/energy expenditure
POMC/CART neurons release (blank) leading to the activation of melanocortin (blank) and (blank) receptors on the PVN.
Simultaneously, (blank) peptide is released and binds an unknown receptor.
They stimulate the PVN regulation pathways that (blank) eating and (blank) energy expenditure
MSH-alpha; MCR3 and MCR4; CART; inhibit; stimulate
Orexigenic neurons release (blank) and (blank) in response to low energy stores.
(blank) is an antagonist of MCR-4 blocking the signaling by α-MSH in the PVN.
AgRP stimulates the release of (blank) resulting in inhibition of POMC.
AgRP; NYP
AgRP;
GABA;
What is the end result of stimulation of AgRP/NYP neurons?
NYP binds to Y1 receptor, alpha-MSH is blocked from binding to MCR-4;
the PVN are not subject to α-MSH binding to MCR-4 and appetite increases, food intake increases, and energy expenditure decreases
Binds to the Y1 receptor and inhibits neuronal function via hyperpolarization thereby interfering with VMN satiety
Preferentially stimulates to desire for CARBOHYDRATES
Reduces fatty acid oxidation, promotes carbohydrate oxidation, and fatty acid synthesis
NYP
Orexigenic
ARC restricted
Colocalizes with NPY neurons in the ARC.
Functional relationship with NPY. Expression is similarly modulated under identical physiological conditions.
Antagonism with melanocortins in eating and body weight control.
AgRP (Agouti-Related peptide)
Hypothalamic neuroendocrine protein.
Part of a family—the pancreatic polypeptide family hormones.
2 gut hormones, pancreatic polypeptide (PP) and peptide tyrosine-tyrosine (PYY) are other members of the family.
Highest levels are found in the ARC.
One of the most potent orexigenic factors.
When you lose weight, it increases.
Stimulates a craving for carbohydrates
NYP
What happens to NYP levels when you lose weight? What does it stimulate a craving for?
they increase; carbohydrates
Found in the lateral and posterior hypothalamic areas with axonal projections throughout the brain.
Receptors are distributed throughout the CNS.
Believed to have a role in the emotional & motivational aspects of feeding behavior.
Increase wakefulness & suppress REM sleep.
Do many things.
orexins
Anorexigenic peptides released in response to food (make you full)
Glucagon-like peptide-1 (GLP-1) Cholecystokinin (CCK) Peptide tyrosine tyrosine (PYY) Pancreatic polypeptide (PP) Oxyntomodulin (OXM or OXY) Insulin Leptin
Released in response to hunger (make you want to eat)
Ghrelin
Galanin
Cortisol
Regulates overall body weight by limiting food intake.
Directly correlate with body fat.
Promotes the synthesis of α-MSH (anorexigenic) suppressing hunger.
Reduces the inhibitory effects of local orexigenic neuropeptide-Y (NPY) on POMC nuclei and suppresses hunger initially but in the long run NPY levels return to normal
Leptin
What does leptin do to food intake & energy expenditure?
decreases food intake
increases sympathetic activity & energy expenditure
Thought to mainly regulate BMR
Increases insulin sensitivity & fatty acid oxidation
Activity is inhibited by adrenergic stimulation & glucocorticoids
Levels are reduced in obese individuals & increased in patients with anorexia nervosa
adiponectin
The largest endocrine organ
Releases hormones, peptide neurotransmitters & growth factors
the gut
Examples of gut hormones
GLP-1 oxyntomodulin CCK ghrelin pancreatic polypeptide PYY
Hormones that stimulate a decrease in blood glucose levels by increasing insulin secretion from the pancreas. Give two examples.
Incretins: glucagon-like peptides, glucose-dependent insulinotropic peptide (GIP)
These are examples of incretins, which decrease blood glucose levels
They potentiate glucose-dependent insulin secretion
Inhibit glucagon secretion
Inhibit gastric acid secretion
Inhibit gastric emptying
Decrease appetite
glucagon-like peptides
This is an incretin (decreases blood glucose by increasing insulin secretion from the pancreas)
Expressed by enteroendocrine K cells of the duodenum & proximal jejunum
glucose-dependent insulinotropic peptide
Overall, what do GLP-1 & GIP do?
decrease appetite & food intake
decrease body weight
A 37 amino acid peptide derived from proglucagon containing the entire 29 amino acids of glucagon.
Synthesized and released in the enteroendocrine L cells of the distal gut.
Secreted in response to food intake within 5-10 minutes.
Has incretin activity.
Is thought to use the GLP-1 receptor.
In the brain it suppresses ghrelin effects.
oxyntomodulin
Expressed mainly in the duodenum and jejunum.
Several active forms (4 major forms)
In human plasma it is the CCK-33 form.
Increases within 15 minutes after eating and peaks at 25 but the half life is only 1-2 minutes.
Binds to GPCRs
Synergistic with leptin
CCK (cholecystokinin)
When CCK binds to GPCRs, what happens?
gallbladder contracts
pancreatic enzymes are released
gastric emptying is inhibited
What are the three pancreatic polypeptide family hormones?
2 gut hormones: pancreatic polypeptide peptide tyrosine tyrosine CNS hormone: Neuropeptide Y (NPY)
It does not cross the blood brain barrier.
It is expressed in the distal GI.
It increases after about 6 hours in proportion to caloric intake.
It increases in response to ghrelin, motilin & gastric distention.
It decreases ghrelin expression.
pancreatic polypeptide
Pancreatic polypeptide increases in response to (blank x3) and decreases (blank) expression
ghrelin, motilin, & gastric distension;
ghrelin
Produced and secreted from enteroendocrine L-cells of the ileum and colon.
Food composition is a potent regulator. Fat leads to the highest levels.
Is a potent agonist of Y1 but predominantly the Y2 receptor (increases POMC and decreases NPY)
Reduces ghrelin, gut motility, delays in gastric emptying, inhibits pancreatic bicarbonate and protein secretion and inhibits gallbladder contraction.
It has satiety effects via actions on the ARC nuclei in the hypothalamus.
protein tyrosine tyrosine
Protein tyrosine tyrosine has (blank) effects via actions of the (blank) nuclei in the hypothalamus
satiety; arcuate
Endogenous agonist of growth hormone
Secretagogue receptor stimulates the release of growth hormone.
Makes you hangry.
Ghrelin
Where is ghrelin secreted? What is essential for the binding of ghrelin & its effects on food intake?
secreted by stomach, small intestine & colon
must be octanolyated (n-octanoic acid side chain)
Ghrelin’s major effect is at the hypothalamus at the (blank) nucleus, where it stimulates (blank) and (blank) causing increased (blank) release inhibiting POMC nuclei
arcuate; NPY; AgRP; GABA
Orexigenic
29 AA peptide
Expressed in the gut and brain (wide distribution) and binds GALR1 in the hypothalamus.
GAL results in a stimulatory effect on feeding
Its effect is small and short lived compared to NPY.
It does not impact food preference.
Galanin
Major hormones produced when you’re hangry =(
ghrelin
Major hormones produced when you’re full =)
insulin (from pancreas)
leptin (from adipose tissue)
CCK, PYY (from intestine)
