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Control of appetite Flashcards

1
Q

What is the distribution of body water?

A

28L intracellular, 14L ECF, 3L plasma

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2
Q

What is plasma oncotic pressure?

A

280-290mOsm/L

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3
Q

What are the two main thirst stimuli?

A

Hypertonic NaCl

Hypertonic glucose

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4
Q

Where are osmoreceptors?

A

Anterior hypothalamus/preoptic area and subfornical organ, OVLT

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5
Q

What is the OVLT?

A

Organum vasculosum of the laminae terminalis (OVLT) is a circumventricular organ located along the ventral part of the anterior wall of the third ventricle.

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6
Q

What is the osmotic threshold for stimulation of thirst/drinking?

A

2-3mOsm

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7
Q

How does the osmotic threshold for vasopressin compare to the osmotic threshold for drinking?

A

About the same

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8
Q

How can low pressure baroreceptors promote thirst? What pathway?

A

Low pressure (volume) receptors induce thirst/drinking via vagus (X), nucleus of tractus solitarius, projections to hypothalamus.

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9
Q

Where does water reach to inhibit drinking?

A

Water in oropharynx / stomach does not stop drinking, while water in duodenum does stop drinking

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10
Q

What osmoreceptors terminate drinking?

A

Duodenal/portal vein osmoreceptors

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11
Q

Why are pre-absorptive mechanisms important for thirst satiation?

A

Drinking ends well before much water is absorbed or plasma OP is restored to normal, therefore pre-absorptive mechanisms are important for thirst satiation.

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12
Q

Babinski-Fröhlich-Syndrome

A

Obesity, hypogonadism, can arise from tumours in hypothalamus (increased appetite and reduced gonadotropin release)

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13
Q

What neurons in the arcuate nucleus regulate appetite?

A

POMC/CART neurons and NPY/AgRP neurons

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14
Q

What happens to the POMC released from arcuate nucleus neurons? What does it act on?

A

POMC is converted into αMSH, which is released onto neurons in PVN that express MC4R leading to stimulation

α-MSH is agonist at this receptor

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15
Q

What do POMC/CART neurons express?

A

Express pro-opiomelanocortin (POMC) and cocaine-and-amphetamine-regulated transcript (CART)

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16
Q

Where else do POMC neurons project to, as well as the PVN?

A

DMN, LHA and VMN

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17
Q

What does POMC/CART stimulation lead to?

A

DECREASES food intake

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18
Q

How do POMC neurons affect metabolism?

A

Increases metabolism, POMC is converted to α-MSH which then stimulates the PVN leading to TRH release

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19
Q

What do NPY/AgRP neurons express?

A

Express neuropeptide Y (NPY) and agouti-related peptide (AgRP)

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20
Q

What happens to the AgRP released from arcuate nucleus neurons? What does it act on?

A

AgRP is released onto neurons in PVN that express MC4R leading to their inhibition

AgRP is endogenous antagonist at this receptor

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21
Q

What does NPY activate?

A

Y receptors

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22
Q

Where else do NPY neurons project to, as well as the PVN?

A

DMN, VMN, LHA

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23
Q

Where are Y receptors?

A

Arcuate

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24
Q

What does NPY/AgRP stimulation lead to?

A

INCREASES food intake

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25
How do NPY/AgRP neurons affect metabolism?
Decrease metabolism, AgRP binds PVN and inhibits neurons, decreases TRH
26
What is the overall role of the POMC/CART neurons?
POMC/CART neurons inhibit feeding/weight gain
27
What is the overall role of NPY, AgRP neurons?
Promote feeding and weight gain
28
What else do NPY/AgRP neurons inhibit?
Inhibit oxytocin-producing neurons in PVN
29
How do POMC/CART and NPY/AgRP neurons know whether or not food intake should take place?
Hormones: from adipose tissue, from pancreas, from GI tract Nutrients: glucose, free fatty acids, amino acids Other neurons
30
What central neurons can affect appetite?
Brain stem (NTS); analysis centres (amygdala, orbitofrontal cortex), other hypothalamic nuclei, reward pathways (VTA)
31
What peripheral neurons can affect appetite?
Oropharyngeal, vision, smell, touch
32
Where is leptin released from?
Adipose
33
What is the leptin receptor?
ObR
34
Where is ObR expressed?
Expressed in POMC/CART (activation stimulates) and NPY/AgRP neurons (activation inhibits)
35
What does leptin binding ObR cause in POMC/CART neurons?
Stimulation - inhibit feeding
36
What does leptin binding ObR cause in NPY/AgRP neurons?
Inhibition - inhibit feeding
37
What is the role of leptin?
Leptin decreases food intake and increases metabolism; long-term regulation of food intake and body weight.
38
Where also express leptin receptors? What is the effect?
VMN (ventromedial nucleus) SF-1 neurons Stimulation decreases food intake
39
Selective deletion of ObR in either VMN or arcuate leads to..
Obese mice
40
Where is insulin released from?
Pancreatic beta cells
41
What role does insulin have in appetite regulation?
Similar to leptin, reduces food intake and increases metabolism
42
Where are insulin receptors and what is the effect of binding?
Insulin receptors expressed in POMC/CART and NPY/AgRP neurons in arcuate Insulin binding stimulates POMC/CART and inhibits NPY/AgRP neurons
43
Where is pancreatic polypeptide released?
Released from pancreatic PP cells in islets of Langerhans
44
When is PP released?
In response to meal (in proportion to caloric intake)
45
Where does PP bind?
Binds to Y4 receptors (GPCR) in brainstem (NTS) and Hypothalamus (Arc, PVN)
46
What nerve may PP act via?
May act via vagus nerve
47
What is the effect of PP binding?
Reduces food intake and increases metabolism
48
What is the only gastric messenger that stimulates food intake and decreases metabolism?
Ghrelin
49
When does ghrelin concentration rise?
[ghrelin] in plasma rises shortly before meal and falls on feeding
50
What happens to ghrelin in individuals with prader willi?
Chronically elevated ghrelin
51
How does ghrelin act and where?
Receptor expressed on NPY/AgRP neurons in arcuate. Stimulates NPY/AgRP and inhibits POMC/CART neurons
52
How do NPY neurons interact with POMC neurons?
NPY/AgRP neurons make GABAergic contacts with POMC/CART neurons
53
Where is peptide tyrosine tyrosine (PYY) made?
Produced in ilium and colon in response to food intake (mainly fat, less so carbohydrates or protein)
54
What are PYY levels in the fasted state?
Low in fasted state and increases following food intake
55
What is the action of PYY?
Binds to Y receptors (GPCRs) in arcuate nucleus and brainstem Decreases food intake
56
What happens to CCK after a meal?
Rises
57
How can glucose sensing occur due to metabolism?
Metabolism of glucose to produce ATP (i.e. change in intracellular [ATP]) KATP: close in response to ATP binding leads to depolarisation AMPK: activated when AMP:ATP increases Allosteric modulation of enzymes by glucose
58
What cells sense glucose?
Glucose-excited cells (GE) Fire action potentials when glucose rises Require glucose metabolism for excitation and switching off of KATP channels Glucose-inhibited cells (GI) Stop firing action potentials when glucose rises
59
Where are glucose sensing cells?
Arcuate, LHA, VMN and NTS
60
How does leucine affect metabolism?
Leucine: selectively activates mTOR which decreases food intake and increases metabolism
61
What amino acids can control food intake?
Essential amino acids: cannot be produced by body and must be taken up by eating. Their presence hence reflects food intake.
62
What does mTOR activation lead to?
Decreased food intake and increased metabolism
63
What inhibits mTOR?
AMP kinase
64
What does AMP kinase promote?
Food intake
65
What appetite receptors are there in the brainstem - what influence do they have?
Leptin receptors in NTS: decreases food intake Ghrelin receptors in NTS: promotes food intake PYY3-36 receptors in NTS: decreases food intake Glucose sensing neurons in NTS: decreases food intake Gastric distention (vagus nerve): decreases food intake
66
Where do brainstem appetite neurons project?
Projects to hypothalamus, particularly ArcN
67
What is the role of the OFC in appetite?
Combines information on taste, smell and visual inputs; texture representation Critical for learning which foods to avoid and which to seek out
68
What is the role of the VTA in food intake?
Reward (dopaminergic neurons, project to nucleus accumbens).
69
What do leptin receptors in the VTA cause?
Decrease [DA] release and increase DA reuptake
70
What do ghrelin receptors in the VTA cause?
Increases [DA] release (reward)
71
What is the role of the NAcc in appetite?
Reward (target of DA neurons from VTA) Cues previously paired with calories elicit neuronal activation, reflecting reinforcing value of food Flavours paired with calories are liked more than flavours not paired with calories
72
What neurons in the lateral hypothalamus help food regulation?
Orexin neurons MCH neurons (melanin concentrating hormone)
73
What do orexin neurons do?
Directly excite NPY/AgRP neurons in ArcN (promote lower metabolism and eating)
74
What do MCH neurons do?
Promote NPY/AgRP release from ArcN (Glucose sensing neurons)
75
What are orexin and MHC neurons responsible for? What inputs are received?
Receives from ARC, VTA, orbitofrontal cortex and striatum. Integrative role: integrates homeostatic, satiety and reward related inputs to modulate feeding behaviour
76
How does the amygdala affect feeding?
Amygdala GABAergic neurons project to LHA glutamatergic neurons Inhibition of these neurons reduces food intake even in starved animals
77
What is thought to underpin obesity?
Resistance to insulin and leptin
78
What can cause leptin resistance?
High fat diet (as opposed to low fat diet with same caloric intake) leads to downregulation of leptin and insulin receptors Reduced transport of leptin across blood brain barrier
79
What does 'lack of leptin' (due to resistance) stimulate? How are POMC/NPY neurons affected?
Lack of leptin signalling induces starvation responses Increased NPY and AgRP expression Changes number and types of synapses on POMC/CART and NPY/AgRP neurons and thereby their activity More excitation of NPY/AgRP neurons and more inhibition of POMC/CART neurons in ob/ob mice Significantly more excitatory and significantly fewer inhibitory synapses on NPY/AgRP neurons in ob/ob mice than in wild type mice Significantly fewer excitatory synapses on POMC/CART neurons in ob/ob mice than in wild type mice
80
What happens to reproductive hormones and thyroid hormone in low leptin/ leptin resistance?
Reduces production of reproductive hormones and hence fertility to prevent pregnancy Decreases thyroid hormone production to slow metabolic rate
81
The action of which of the following in the ventromedial hypothalamus will cause a dose dependent decrease in food intake and, over a period of weeks, decreased body weight?
Insulin/Leptin
82
Conversely the administration of which of the following, either centrally or peripherally, will increase food intake and body weight and decrease fat utilization in rodents?
Ghrelin
83
The orexigenic action of ghrelin is thought to act on the hypothalamic
Arcuate nucleus
84
Ghrelin activates neurons containing
NPY
85
Which of the following targets the same hypothalamic site as ghrelin but suppresses food intake?
Leptin
86
Which of the following brain peptides cause the greatest increase in feeding?
Agouti-related peptide
87
A gut hormone with tyrosine residues at either end, known as... is able to enter the brain at the ArcN to regulate appetite via non-saturable mechanisms.
PYY

Applied physiology and pharmacology (18 decks)

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