Gastro appetite Flashcards
is obesity associated with high or low income countries?
low
-> historically was high
3 triggers for thirst
- body fluid osmolality
- blood volume reduction
- blood pressure is reduced
what is the most potent of the 3 triggers for thrist?
body fluid osmolality
Plasma osmolality increase is the more potent stimulus – 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
hormone that controls osmolality
ADH/ vasopressin
where does ADH act?
aquaporin 2 of the collecting duct (increase of aquaporin 2 insertion on membrane), acting on the kidney
what happens when ADH is low?
large volume of urine is excreted (water dieuresis)
what is the term for when lots of ADH prevents excretion of large volumes of dilute urine?
anti-diuresis
where is ADH stored in the body?
the posterior pituitary gland
what receptors measure osmolality? Where are they found?
- osmoreceptors
- found in the hypothalamus
in which regions of the hypothalamus are osmoreceptors found? (2)
- organum vasculosum of the lamina terminalis
2. subfornical organ
what happens to osmoreceptors when solution is hypertonic
Cells shrink when plasma more concentrated (lower plasma osmolality)
Proportion of cation channels increases – membrane depolarizes
Send signals to the ADH producing cells to increase ADH
Fluid retention
Invokes drinking
Where are receptors for thirst located?
How long does the thirst sensation last at these receptors?
receptors in the: 1. mouth 2. pharynx 3. oesophagus Relief of thirst sensation via these receptors is short lived.
when is thirst completely satisfied?
once plasma osmolality is decreased/blood volume/arterial pressure corrected
what system controls blood pressure/volume
renin-angiotensin-aldosterone system
which cells are activated by low BP?
juxtaglomerular cells of renal afferent arterioles: leads to production of renin
what does renin release cause?
production of angiotensin I (renin is an enzyme that cleaves angiotensinogen to form angiotensin I)
what is angiotensin I converted into in the blood?
angiotensin II
-> facilitated by ACE in the lungs
what does angiotensin II promote?
- vasoconstriction - increase sympathetic activity
- thirst
- ADH secretion
- Aldosterone release (from zona glomerulosa)
what does aldosterone do in the renin-angiotensin-aldosterone system?
H2O retention via Na+Cl- absorption and K+ excretion
which structure is most important in regulating appetite?
the hypothalamus
hormones that regulate appetite?
GHRELIN
PYY
LEPTIN
other than hormones, what can influence how the hypothalamus regulates appetite?
neural input from the periphery and other brain regions via vagus
what does orexigenic mean?
appetite stimulant
what does anorectic/anorexigenic mean?
appetite suppresive
structures of the hypothalamus (4)
- arcuate nucleus
- ventromedial hypo
- lateral hypo
- paraventricular nucleus
where do the orexigenic/anorectic neurons of the arcuate nucleus feedback to in the hypothalamus?
What is this structures role?
the paraventricular nucleus
Fibres project to posterior pituitary (release of oxytocin and ADH)
how does the arcuate nucleus control appetite?
through orexigenic and anorectic neurons
Where does the paraventricular nucleus project to?
Posterior pituitary where in releases ADH and oxytocin
what is the ventromedial hypothalamus associated with?
satiety -> lesions in the this region in rats leads to severe obesity
What does POMC (pro-opiomelanocortin) do to the arcuate nucleus?
activates it = lower food intake
What does the lateral hypothalamus produce?
only orexigenic peptides
examples of chemicals that affect appetite?
endocannabinoids, AMPK, tyrosine phosphatase
what does the arcuate nucleus produce?
peptides: orexigenic peptides and anorectic peptides
What feature of the arcuate nucleus means that it is able to access peripheral hormones
Incomplete blood brain barrier
What does the arcuate nucleus integrate
peripheral and central feeding signals
what are the two neuronal populations of the arcuate nucleus?
stimulatory (NPY/AGRP)
inhibitory (POMC)
What does leptin stimulate in the arcuate nucleus?
What is its effect?
POMC/CART neurons
High leptin stimulates these neurons to decrease feeding and produce satiety
NPY/Agrp neuron have receptors for what hormones?
What is their action?
When are they activated?
leptin and insulin
Leptin inhibits NPY/AGRP
Inc. NPY/AGRP signalling stimulates food intake
->activated when leptin is decreased e.g. when fasting, have uncontrolled diabetes or genetic leptin deficiency
what systems other than GI is the arcuate nucleus involved in?
fertility and cardiovascular regulations
When POMC is stimulated, what is created?
production of a-MSH (a melanocortin)
This leads to production of MC4R
what are MC4-receptors stimulated by?
What is their action?
serotonin to reduce appetite and food intake
are any NPY or Agrp mutations associated with appetite in humans?
none discovered
deficiency in what can cause morbid obesity?
POMC
mutation to what receptor can cause morbid obesity?
MC4-R
why is the amygdala important for appetite
involved in emotion, memory -> reward pathways
-> contributes to appetite
what does the lateral hypothalamus produce that affects appetite?
appetite stimulants
What does the adipostat mechanism do?
keep fat mass within a narrow range
What is the adipostat mechanism?
Circulating hormone produced by fat
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 ?
how many neural pathways are associated with the adipostat mechanism?
2 hypothalamic neural pathways
where is leptin made?
by adipocytes in white adipose tissue + enterocytes
How does leptin travel?
in the body plasma
where does leptin act in the hypothalamus?
What is its effect?
the arcuate nucleus
Regulates appetite and thermogenesis (expenditure)
What are high levels of leptin associated with?
Atherosclerosis development via innate system
What conditions are low levels of leptin associated with?
depression
Alzheimer’s
features of congenital leptin deficiency
normal birth weight
excessive eating = early childhood obesity
Rare
How is body fat associated with serum leptin?
Inc. serum leptin in obese subjects suggests obese subjects become insensitive to leptin
3 ways which leptin can fail:
- insufficient production -> deficiency
- leptin resistance -> like T2DM: inability to detect satiety despite high energy store
- regulatory defect -> low leptin despite high BMI
WHat can leptin resistance lead to?
Obesity due to leptin resistance- hormone is present but doesn’t signal effectively
Why do we feel less hungry after meal?
- bulk in tum
- nutrients in circulation
- Hormones from gut
hormones in gut (3)
2 GI hormones that control appetite and their actions?
Ghrelin
Stimulates appetite, increases gastric emptying
Peptide YY
Inhibits food intake
what secretes the GI hormones?
enteroendocrine cells in the stomach, pancreas and SB
what do GI hormones do?
control various functions of digestive organs (motility, appetite, satiety)
When are blood levels of ghrelin highest? What happens?
before meals
- > help prepare for food intake by inc gastric motility and acid secretion
- > increases appetite
which nucleus does ghrelin directly modulate?
the arcuate nucleus
- > stimulates NPY/Agrp neurons
- > inhibits POMC
what does ghrelin regulate
-> involved in regulation of reward, taste sensation, memory and circadian rhythm
what type of rhythm does ghrelin have?
diurnal- this plays a role in meal regulation
How has ghrelin been proven to increase food intake?
In rats: rats given ghrelin for 7 days - cumulative inc in food intake
In humans: subjects given iV ghrelin or IV saline and given all you can eat buffet. Inc. energy consumption in subjects given ghrelin
what does PYY stand for?
peptide tyrosine tyrosine
where and when is PYY released?
from the terminal ileum and colon in response to feeding
what types of food induce best PYY response
wholegrain food, fish proteins + fibre
what does PYY do to appetite?
reduces it
-> can be digested or injected IV
whatt does PYY release inhibit release of?
NPY
which neurons are stimulated by PYY?
POMC
what can PYY cause at higher dose?
nausea and fullness
-> food intake reduction is dose dependent
examples of comorbidities obesity is associated with?
Depression- 1/3 of patients with BMI over 30 Sleep apnoea- narrowing of trachea Bowel cancer- proven** Osteoarthritis Gout PVD Diabetes Hypertension MI Stroke
How does environment and genetic susceptibility to obesity affect BMI?
not being genetically susceptible and in healthy environment has little impact on BMI
Being genetically prone and in a toxic environment increases BMI significantly
what is the difference in how you observe leptin vs PYY satiety?
leptin = longer term PYY = immediate
Describe weight homeostasis
Weight augmented (overfed): -Inc. sympathetic nervous system activity -Inc. energy expenditure -Dec. hunger/food intake -Weight loss Weight reduced (underfed state) -Dec. sympathetic nervous system activity -Dec. energy expenditure -Inc. hunger/food intake -Weight gain
How does leptin levels change with body fat?
How has this been scientifically proven?
Low with low body fat
High with high body fat
Replacement of leptin in ob/ob mouse decreases weight
