appetite Flashcards
what are three main triggers that control thirst?
Body fluid osmolality
Blood volume is reduced
Blood pressure is reduced
what is the most potent stimulus of thirst?
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)
how does the body regulate osmolality?
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).
how does the body measure osmolaloty?
osmoreceptors
Sensory receptors
Osmoregulation
Found in the hypothalamus:
Organum vasculosum of the lamina terminalis (OVLT)
Subfornical Organ (SFO)
how is ADH release regulated by osmoreceptors?
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)
how do we sense thirst, and prevent overdrinking?
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.
how are changes in blood pressure and volume controlled?
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
what are the effects of angiotensin II?
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
what are the basic principles of body weight homeostasis?
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
what does the central circuit do?
defends agains reduction of body fat
(What system defend against rapid expansion?
Yet to be discovered)
how is appetite regulated?
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
what parts of the hypothalamus effect appetite?
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
what is the arcuate nucleus?
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)
what is the melanocortin system?
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
what human CNS mutations affect appetite?
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.
what other regions of the brain influence appetite?
higher centres
Amygdala- emotion, memory, reward
Other parts of the hypothalamus, e.g. lateral hypothalamus
Vagus to brain stem to hypothalamus.
what is the adipostat mechanism?
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 ?
what is leptin?
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
what is congenital leptin deficiency?
(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
what is a summary of the systemic effects of leptin?
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
what is the mechanism of action of leptin dysfunction?
three
- insuficient production
- regulatory signalling may be defective and reduce leptin levels despite high body fat
- leptin resistance
what is leptin resistance?
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.
why do we fell less hungry after a meal?
NOT bulk in stomach
NOT nutrients in circulation
YES - hormone signals from the gut
what are gastrointestinal hormones?
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
