Satiety Flashcards
Define orexigen [1]
Define anorexigen [1]
orexigen: A substance that increases food intake / appetite stimulant. Can be a hormone or drug
Anorexigen: A substance that inhibits food intake
What are ingested nutrients within the GI tract detected by? [1]
GPCRS in the GI tract
Which cels in the GI tract sense the luminal envrionment? [1]
Describe how their structure is adapted to their role
Enteroendocrine Cells:
Apex: Long processes into lumen + microvilli: for sampling the luminal nutrient environment.
Basal side: stores many vesicles, containing appetite regulating hormones. close to nerve endings - hormones bind to nerve receptors to signal orexigenic or anorexigenic pathways
Describe MoA of nutrients in GI releasing signal molecules
Nutrient binds to GPCR on apex of ECC
Signals release of hormone on basal side of cell, via intracellular pathway.
Binds to receptors on afferent nerves (eg. The vagus nerve): increases/decreases firing.
Role of the following of on firing of ECC vesicles?
5HT [1]
Leptin [1]
Ghrelin [1]
5HT - increases firing
Leptin - decreases firing
Ghrelin - decreases firing
How does VN work in appetite regulation with regards to chemoreceptors and mechanoreceptors? [2]
Where does VN stimulate in the brain with ^ information? [1]
Chemoreceptors: activated by mediators released from EEC cells (nutrients / hormones / pH etc)
Mechanoreceptors: detect stretch (gastric distention causes satiety)
Goes to NTS
What effect does increased release of leptin indicate? [1]
Describe release of leptin throughout day [1]
What effect does increased release of leptin indicate? [1]
Increases satiety / makes you feel full
Describe release of leptin throughout day [1]
Duirnal - not related to food intake
How does leptin affect:
NPY / AgRP neurones [1]
POMC / CART neurones [1]
Is it a short or long term acting hormone? [1]
How does leptin affect:
NPY / AgRP neurones: inhibits
POMC / CART neurones: activates
Is it a short or long term acting hormone: long term
Why can’t leptin be used as a clinical drug target?
Obese people have high leptin levels: leptin resistant so giving leptin to these individuals won’t reduce hunger.
Can be used in congenitally leptin-deficient children.
PYY has what effect on satiety? [1]
PYY leads to enhanced satiety
Which cells release PYY? [1]
Where is PYY predominately found? [1]
What effect does PYY have on NPY [1] and POMC neurones [1]
Which cells release PYY? [1]: L cells in GI tract
Where is PYY predominately found: Colon –> rectum
What effect does PYY have on NPY: inhibits
and POMC neurones: activates
PYY is released in response to which nutrients circualting at high levels?
Protein & Fat
MoA of PYY:
Different receptors respond to PYY:
What do Y1-5 receptors cause an effect on? [3]
What does Y2 receptor respond to? [1]
High levels of PYY are linked to feeling WHAT? [1]
MoA of PYY:
Different receptors respond to PYY:
What do Y1-5 receptors cause an effect on: expressed peripheral/vagal/central
What does Y2 receptor respond to? [1]: primary receptor mediating effects
Linked to feelng nauseaus
Is insulin an acute or long term satiety signal? [1]
Insulin effect on NPY/AgRP neurones [1]
Insulin effect on αMSH/CART? [1]
Is insulin an acute or long term satiety signal: acute
Insulin effect on NPY/AgRP neurones: inhibts
Insulin effect on αMSH/CART: activates
GLP-1 is released in response to? [1]
Effect of GLP-1 on blood glucose? [1]
What is GLP-1 like in obese patients? [1]
GLP-1 is released in response to? [1]
Food intake
Effect of GLP-1 on blood glucose? [1]
Decreases blood glucose levels
What is GLP-1 like in obese patients? [1]
Reduced in obese patients
Effect of pancreatic polypeptide (PP) on appetite? [1]
Effect of oxontymodulin on appetite? [1]
pancreatic polypeptide (PP): anorexigenic (decreases appetite)
Oxontymodulin: anorexigenic: decreases ghrelin levels in plasma
Which hormone is the major peripheral orexigenic hormone? [1]
Which cells in the body secrete this hormone? [1]
Ghrelin: major hunger hormone
Secreted from alpha cells in the stomach
Ghrelin is [] in proportion to the calories ingested
Ghrelin is suppressed in proportion to the calories ingested
How does ghrelin increase hunger? [3]
Glucose homeostasis, gut motility, pancreas function, inflammation
Act directly at hypothalamus: via VN
Short and long term actions of initiating hunger
Name the neuroendorcine neurones in the brain that control hunger [4]
Where are they located in the brain? [1]
2 groups of neuroendocrine neurones:
- Neuropeptide Y (NPY) and Agouti related peptide (AgRP) respond to orexigens:
- Cocaine and Amphetamine related transcript (CART) and pro-opiomelanocortin (POMC)- anorexigens
Located in the arcuate nucleus of hypothalamus
AGRP/NPY neurones in arcuate nucleus of hypothalamus are activated by which hormone? [1]
What biochem effect does this have? [1]
AGRP/NPY neurones in arcuate nucleus of hypothalamus are activated by which hormone? [1]
Ghrelin
What biochem effect does this have? [1]
Causes a release of Y1 receptors
POMC/CART neurones in arcuate nucleus of hypothalamus are activated by? [2]
What biochem effect does this have? [1]
Activated by insulin and leptin [2]
Decrease food intake by releasing melanocortins:
Main is α-melanocortin-stimulating hormone (α-MSH)
Label A-E xx
A: GLP-1
B: PYY
C: Ghrelin
D: Leptin
E: Insulin
Role of malonyl-coA? [1]
[] malonyl-coA supresses food intake
[] malonyl coA increases food intake
Malonyl-CoA is the substrate for fatty acid synthase, but it is a key determinant for the entry of fatty acids into the mitochondria, and appears to play a pivotal signaling role in appetite regulation.
Increased malonyl-coA supresses food intake
Decreased malonyl coA increases food intake
Role of Malonyl CoA? [1]
What determines ^?
Malonyl CoA is a relay in energy homeostasis
Determined by AMP/ATP ratio (energy levels), and AMPK CPT1c relays the signal
Explain how overall food intake decreases in response to increased energy levels? [1]
Explain how ^ occurs [3]
Increased M-CoA - stimulates FA synthesis –» therefore suppresses appetite
More ATP over AMP -> increased denovo FA synthesis -> increased M-CoA -> stimulation of POMC/CART + suppression NYP/AgRP -> decreased food intake
Effect of serotonin on appetite?
Effect on POMC and AgRP neurones?
Serotonin (5HT): anorexigenic: augmentation of brain 5HT inhibits food intake, depletion promotes weight gain
They increase signalling (simulate) activity in the POMC neurones (via the 5HT2CR)
They decrease signalling in the AgRP neurones (via the 5HT1BR)
FYI
Antidepressants can cause weight gain and loss
Neuroendocrine pathways used to treat dietary disturbance?
Cannabis found to increase food intake. So CB1 receptor antagonists tried as obesity treatment. Withdrawn due to side effects.
NO drug treatments for obesity currently.
Treatments focused on lifestyle/behaviour modification.
Final line treatment is bariatric surgery
Despite our knowledge of neurophysiology, we do not have a successful pharmacological treatment for obesity
