appetite Flashcards

1
Q

what are three main triggers that control thirst?

A

Body fluid osmolality

Blood volume is reduced

Blood pressure is reduced

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2
Q

what is the most potent stimulus of thirst?

A

plasma osmolality

change of 2-3% induces strong desire to drink
(Decrease of 10-15% in blood volume or arterial pressure is required to produce the same response)

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3
Q

how does the body regulate osmolality?

A

Antidiuretic hormone (ADH) or arginine vasopressin (from the posterior pituitary)

Acts on the kidneys to regulate the volume & osmolality of urine
Collecting duct - Aquaporin 2 channel

When plasma ADH is low a large volume of urine is excreted (water diuresis)

When plasma ADH is high a small volume of urine is excreted (anti diuresis).

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4
Q

how does the body measure osmolaloty?

A

osmoreceptors

Sensory receptors

Osmoregulation

Found in the hypothalamus:
Organum vasculosum of the lamina terminalis (OVLT)

Subfornical Organ (SFO)

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5
Q

how is ADH release regulated by osmoreceptors?

A

Cells of osmoreceptors shrink when plasma more concentrated (hypertonic?)

->

Proportion of cation channels increases – membrane depolarizes

->

Send signals to the ADH producing cells to increase ADH

->

Fluid retention
Invokes drinking

and vice versa (less firing then plasma concentration is low and the cells expand, so less ADH is released, and more water is excreted)

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6
Q

how do we sense thirst, and prevent overdrinking?

A

Thirst is decreased by drinking even before sufficient water has been absorbed by the GI tract to correct plasma osmolality

Receptors in mouth, pharynx, oesophagus are involved

Relief of thirst sensation via these receptors is short lived.

Thirst is only completely satisfied once plasma osmolality is decreased or blood volume or arterial pressure corrected.

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7
Q

how are changes in blood pressure and volume controlled?

A

Renin-angiotensin-aldosterone system

BP drops ->
detected by juxtaglomerular cells of renal afferent arteriole->
secretion of renin from the JGA

renin activates system by cleaving angiotensinogen (in the liver)
->
angiotensin I
->
converted into Angiotensin II by angiotensin converting enzyme (ACE) in the lungs

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8
Q

what are the effects of angiotensin II?

A

Vasoconstriction, increase sympathetic activity

Thirst

ADH secretion

production of aldosterone from the zona glomerulosa of the adrenal cortex - leads to potassioum secretion and sodium absorbtion
->
H2O retention via
Na+CL- absorption and K+ excretion

all of this raises blood pressure and volume

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9
Q

what are the basic principles of body weight homeostasis?

A

Passmore 1971 – most individual adults maintain a relatively stable weight over long periods

A reduction in fat mass increases food intake and reduces energy expenditure

Adipose tissue expansion reduces food intake and increases energy expenditure

weight augmented:
increased sympathetic activity
increased energy expenditure
decreased hunger

weight reduced:
decreased sympathetic activity
decreased energy expenditure
increased hunger
decreased thyroid function
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10
Q

what does the central circuit do?

A

defends agains reduction of body fat

(What system defend against rapid expansion?
Yet to be discovered)

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11
Q

how is appetite regulated?

A

regulated in the hypothalamus

hormones: Ghrelin, PYY, other gut hormones

Neural input from the periphery and other brain regions

Leptin

these all act via the vagus nerve
towards the hypothalamus

leads to increased/decreased food intake and increased/decreased energy expenditure

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12
Q

what parts of the hypothalamus effect appetite?

A

the arcuate nucleus (medial, basal part)

sits adjacent to the third ventricle

the arcuate nucleus produced both:
orexigenic (appetite stimulant)
anorectic (appetite repressive)
peptides

orexigenic and anorectic neurones project to the paraventricular nucleus of the hypothalamus. this contains neurones that project to the posterior pituitary, where ADH is produced

the lateral hypothalamus only produces orexigenic peptides

the ventromedial hypothalamus is associated with satiety (anorectic). lesions in this region lead to extreme obesity

arcuate nucleus also produces proopio melanocortin (POMC) which decreases food intake

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13
Q

what is the arcuate nucleus?

A

Brain area involved in the regulation of food intake

Incomplete blood brain barrier, allows access to peripheral hormones.

Integrates peripheral and central feeding signals
Two neuronal populations:

Stimulatory (NPY/Agrp neuron)
Inhibitory (POMC neuron)

(NPY= neuropeptide Y)
(Agrp= agouti related peptide)
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14
Q

what is the melanocortin system?

A

part of the central nervous system circuits

melanocortins are products of POMC (eg. a-MSH)

melanocortin 4 receptors (MCR4) are expressed on paraventricular cell
these receptors are stimulated by serotonin

this leads to reduction in appetite and weight, and decreased food intake

the melanocortin system is INHIBITORy

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15
Q

what human CNS mutations affect appetite?

A

No NPY or Agrp mutations associated with appetite discovered in humans.

POMC deficiency and MC4-R mutations cause morbid obesity.

Mutations not responsible for the prevalence of obesity - but useful to explain signalling.

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16
Q

what other regions of the brain influence appetite?

A

higher centres

Amygdala- emotion, memory, reward

Other parts of the hypothalamus, e.g. lateral hypothalamus

Vagus to brain stem to hypothalamus.

17
Q

what is the adipostat mechanism?

A

Circulating hormones produced by fat, the more adipose tissue, the more hormones

Hypothalamus senses the concentration of hormone.

Hypothalamus then alters neuropeptides to increase or decrease food intake.

Perhaps a problem with the regulation of the adipostat mechanism leads to obesity ?

18
Q

what is leptin?

A

Meaning - thin (leptos-greek)

Discovered in 1994.

Missing in the ob/ob mouse.

Made by adipocytes in white adipose tissue, and enterocytes

Circulates in plasma.
Acts upon the

hypothalamus regulating appetite (intake) and thermogenesis (expenditure).

low levels of leptin also play a role in the development of atherosclerosis, alzheimers, depression

19
Q

what is congenital leptin deficiency?

A

(In these children leptin has been effective in reducing body weight.) (does this mean as a treatment?)

Only few people known to have this defect.

they have very low serum levels of leptin, and are therefore always hungry

20
Q

what is a summary of the systemic effects of leptin?

A

low when low body fat

high when high body fat

replacement in the ob/ob mouse decreases weight

hormone that decreases food intake and increases thermogenesis

21
Q

what is the mechanism of action of leptin dysfunction?

A

three

  1. insuficient production
  2. regulatory signalling may be defective and reduce leptin levels despite high body fat
  3. leptin resistance
22
Q

what is leptin resistance?

A

Leptin circulates in plasma in concentrations proportional to fat mass

Fat humans have high leptin

Obesity due to leptin resistance- hormone is present but doesn’t signal effectively

Leptin is ineffective as a weight control drug.

23
Q

why do we fell less hungry after a meal?

A

NOT bulk in stomach

NOT nutrients in circulation

YES - hormone signals from the gut

24
Q

what are gastrointestinal hormones?

A

Secreted byenteroendocrine cellsin thestomach, pancreas & SB

Control various function of digestive organs

Appetite regulation by :

Ghrelin
Stimulates appetite, increases gastric emptying

Peptide YY
Inhibits food intake

25
Q

what is ghrelin?

A

Blood levels of ghrelin are highest before meals.
help prepare for food intake by increasing gastric motility and acid secretion

Directly modulates neurons in the arcuate nucleus
Stimulates NPY/Agrp neurons.
Inhibits POMC neurons.

Increases appetite

Regulation of reward, taste sensation, memory, circadian rhythm

(ignoring peaks before meals it has a diurnal rhythm, peaking at 1am, lowest at 9am)

makes you eat more if injected
(stimulatiry)

26
Q

what is PYY?

A

Peptide tyrosine tyrosine (PYY)

Short peptide released in the terminal ileum (TI) and colon in response to feeding (36 Amino acids)

Reduces appetite – can be digested or injected IV

Food arriving to the TI and colon results in PYY release
especially wholegrains and fibre

Inhibits NPY release

Stimulates POMC neurons

(inhibitory)

27
Q

what comorbidities are associated with obesity?

A
depression
stroke
sleep apnoea
bowel cancer
osteoarthritis
gout
hypertension
diabetes
peripheral vascular disease
28
Q

how is obesity prevalence changing?

A

over past 30 years has got a lot worse