Flashcards in Lecture 31 - Feeding and Weight Control Deck (58):
1
Peripheral signals involved in weight control
1)
2)
3)
1) CCK
2) Leptin
3) Ghrelin
2
Hypothalamic chemicals involved in weight control
1)
2)
3)
1) Neuropeptide Y
2) POMC
3) Agouti-related peptide
3
Adiposity signals
Leptin
Insulin
Act long-term
4
Peptides that increase food intake
1)
2)
3)
4)
5)
6)
1) Neuropeptide Y
2) Melanin concentrating hormone
3) Agouti-related peptide
4) Orexin A and B
5) Endocannabinoids
6) Ghrelin
5
Peptides that increase food intake that act in the brain
1)
2)
3)
4)
5)
1) Neuropeptide Y
2) Melanin concentrating hormone
3) Agouti-related hormone
4) Orexin A and B
5) Endocannabinoids
6
Peptides that increase food intake that act in the periphery
Ghrelin
7
Peptides that decrease food intake
1)
2)
3)
4)
1) a-melanocyte stimulating hormone
2) CART
3) Leptin
4) Cholecystokinin
8
Peptides that increase food intake that act on the brain
Alpha-melanocyte stimulating hormone
9
Peptides that increase food intake that act in the periphery
CART
Leptin
Cholecystokinin
10
Where is CCK produced, and in response to what?
Produced by gut
Released in response to digestion of certain nutrients, particularly fat
11
What does CCK act on?
Binds to CCKa receptor on vagus nerve.
This transmits information to nucleus tractus solitarius in medulla.
This transmits to hypothalamus to terminate a meal.
12
How does CCK stimulation of vagus nerve affect the brain?
Ascending signal passes through nucleus tractus solitarius to hypothalamus.
Acts on hypothalamus to terminate a meal.
13
Where is ghrelin secreted?
By stomach
14
When do ghrelin levels rise?
Pre-prandially
15
What are ghrelin plasma levels inversely-proportional to?
BMI
16
Effect of increased ghrelin on appetite
Increases appetite
17
Ghrelin receptor name and locaiton
GHSR-1a, located in hypothalamus
18
Effect of increasing CCK level in rats
More frequent, smaller meals. Not much effect on weight.
19
Does ghrelin quickly or slowly modulate hunger?
Quickly
20
What secretes leptin?
Adipocytes
21
What are plasma leptin levels inversely proportional to?
BMI, adiposity
22
Effect of increased leptin on hunger
Decreases hunger
23
How does leptin enter the brain?
Via transporter across the blood brain barrier
24
Parts of hypothalamus that are involved in hunger
Arcurate nucleus
Paraventricular nucleus
25
Arcurate nucleus role in hunger
Contains cell bodies of neurons that project to paraventricular nucleus
26
Hunger-related neurons in arcurate nucleus
1)
2)
1) POMC/CART neurons. When stimulated, reduce food intake
2) Neuropeptide Y/Agouti-related peptide neurons. When stimulated, increase food intake.
27
Neurons that release factors that increase food intake
Neuropeptide Y/Agouti-related peptide neurons in the arcurate nucleus of the hypothalamus
28
Neurons that release factors that decrease food intake
POMC/CART neurons in the arcurate nucleus of the hypothalamus
29
Effect of leptin on the arcurate nucleus
Stimulates POMC/CART neurons, inhibits NPY/AGRP neurons. This results in reduction of food intake.
30
Members of the pancreatic polypeptide family
1)
2)
3)
1) Neuropeptide Y (synthesised in CNS)
2) Peptide YY (GIT)
3) Pancreatic polypeptide (pancreatic islets)
31
Highly-conserved neuropeptide involved in food intake regulation
Neuropeptide Y
32
NPY effects
1) Potent stimulator of appetite
2) Reduces energy expenditure
33
Where does NPY act?
On the hypothalamus (paraventricular nucleus)
34
NPY receptors
1)
2)
3)
1) All GPCR
2) Y1, Y5 involved in appetite stimulation. Located post-synaptically
3) Y2 is an autoreceptor. Located presynaptically, regulates NPY release
35
What regulates release of NPY?
Leptin
36
POMC
Pro-opiomelanocortin
A precursor protein to several neurotransmitters
37
Important cleavage product of POMC in hunger regulation
Alpha-melanocortin stimulated hormone
38
Release pattern of a-MSH
Tonically-released, therefore tonically inhibits food intake
39
POMC localisation in CNS
Limited to arcurate nucleus and nucleus tractus solitarius.
Colocalised with other neuropeptides in arcurate nucleus
40
What cleaves aMSH from POMC?
Prohormone convertases (PC1 and PC2)
41
POMC receptor
Melanocortin receptors 1 to 5 (MC1-5R).
GPCR
42
aMSH receptor
MC4R.
43
From where is aMSH released?
Paraventricular nucleus
44
Effect of aMSH
Increases energy expenditure
45
What regulates aMSH?
Leptin, feeding status
46
Agouti-related peptide location in CNS
Synthesised in arcurate nucleus.
Co-localised with NPY
47
What does AGRP bind to?
It is an endogenous antagonist of MC4R
48
Endogenous agonist of MC4R
aMSH
49
Endogenous antagonist of MC4R
AGRP
50
Effect of AGRP
Inhibits aMSH by binding to MC4R.
Increases food intake, reduces energy expenditure
51
Effect of decreased leptin expression
1)
2)
3)
4)
1) Decreased leptin action in the hypothalamus
2) Inhibition of POMC neurons, which results in less aMSH
3) Activation of NPY/AGRP neurons in arcurate nucleus. Increased NPY/AGRP release to PVN. AGRP blocks aMSH action.
4) Increased food intake, decreased energy expenditure
52
Effect on hypothalamus of ghrelin
Stimulates AGRP/NPY neurons in arcurate nucleus
53
Adoption studies of BMI
BMI of adopted child closer to biological parents than adoptive parents
54
Major contributing factor to obesity epidemic
Hedonic systems involved in eating palatable food
55
Pathway activated in response to palatable food
Mesolimbic dopaminergic system (the same one that is involved in addiction)
56
Areas involved in hedonic mesolimbic dopaminergic system
Ventral tegmental area and nucleus accumbens
57
Effect of leptin on mesolimbic system
Inhibits activity of VTA dopaminergic neurons, which express leptin receptors
58