Appetite Regulation Flashcards
what are the stimuli for thirst
which is the most potent
increase in plasma osmolality
reduction in blood volume
reduction in blood pressure
increased plasma osmolality is the most potent
a 2-3% increase in plasma osmolality induces strong desire to drink
a 10-15% decrease in blood volume or blood pressure is needed to induce the same strong desire to drink
how is plasma osmolality regulated
plasma osmolality increases → osmoreceptors in organum vasculosum and subfornical organ (in hypothalamus) shrink → increases the proportion of active cation channels on cell membrane → +ve charge influx → membrane depolarises
osmoreceptors send APs which stimulate ADH release from posterior pituitary
ADH enters blood → travels to kidney
ADH binds to V2 receptor on collecting duct → triggers vesicles of Aquaporin 2 channels to insert themselves into apical membrane
increased water reabsorption → small volume of concentrated urine is released
plasma osmolality decreases → osmoreceptors swell → cation channels inactive → hyperpolarisation → no APs can be generated → no ADH is released
less water reabsorbed in collecting duct → large volume of dilute urine is produced
Note: cation channels are inactivated by stretch
what is important to note about the reasons someone may feel thirst
not always physiological → e.g. not always due to high plasma osmolality/low blood pressure/low blood volume
can be prompted by habit, alcohol, caffeine, drugs, wanting warming or cooling drinks
what is the issue that arises surrounding being relieved of thirst after drinking
how is this overcome
there is a delay between the absorption of water in the GI tract and the correction of plasma osmolality (takes time for the water absorbed to then circulate around the body) → therefore there needs to be a mechanism in place to prevent over drinking
therefore thirst is decreased by drinking before sufficient water has been absorbed by the GI tract to correct plasma osmolality
receptors in mouth, pharynx, oesophagus provide short lived relief of thirst sensation when you drink
however thirst is only completely satisfied once plasma osmolality/blood volume/blood pressure has been corrected
where are the receptors which provide relief from thirst
why are they necessary
mouth, pharynx, oesophagus
time delay between the absorption of water in the GI tract and the correction of plasma osmolality/blood volume/blood pressure which stops the person feeling thirsty anymore/complete satisfaction of thirst
the receptors provide short lived relief of thirst to prevent over drinking/ fluid overload because that can interfere with nutrient absorption as it can cause hyponatremia (and much of the nutrient transport is driven by sodium) and it is a waste of energy for the kidneys to filter all the excess fluid
how are changes in blood pressure or blood volume corrected
via the renin-angiotensin-aldosterone system
reduced blood pressure/blood volume → reduction in renal perfusion pressure → detected by baroreceptors → juxtaglomerular cells release renin
(NOTE: renin release can also be stimulated by reduced Na+ delivery to DCT and this is detected by macula densa or increased sympathetic stimulation of JGA cells via B1 adrenergic receptors)
renin cleaves angiotensinogen (produced by liver) → angiotensin I
angiotensin I is cleaved by Angiotensin Converting Enzyme (ACE is mainly produced by lungs and this process occurs in lungs) → angiotensin II
angiotensin II:
induces thirst
stimulates ADH secretion → increased H2O reabsorption
stimulates sympathetic nervous system → vasoconstriction → increased blood pressure
stimulates release of aldosterone from zona glomerulosa in adrenal cortex
aldosterone acts on cells n DCT → increased Na+ reabsorption and K+ excretion → water retention
blood pressure/blood volume increases
what is the clinical importance of RAAS
ACE inhibitors, ARBs and direct renin inhibitors are used to treat hypertension
describe weight homeostasis
changes to adipose tissue activate responses which favour the return to their previous/original weight
if fat mass reduces or person is underfed → activates systems which:
reduce energy expenditure
reduce sympathetic activity
reduce energy expenditure
increase hunger/food intake
decrease thyroid function
in order to cause subject to gain weight
if fat mass increases or person is overfed → activates systems which:
increase energy expenditure
increase sympathetic activity
increase hunger/food intake
in order to cause weight loss
outline how peripheral stimuli influence appetite
through the hypothalamus
hypothalamus links higher brain centres e.g. amygdala and peripheral neuronal input and hormones e.g. leptin, ghrelin and PYY
peripheral neuronal input is via the vagus nerve to brainstem → brainstem communicates with hypothalamus → hypothalamus communicates with higher brain centres
nuclei in hypothalamus have incomplete blood brain barrier → hormones from the periphery in the systemic circulation can act on hypothalamic neurons
hypothalamus generates a response to the information from peripheral stimuli to influence food intake and energy expenditure
what are the different areas of the hypothalamus involved in appetite regulation
what do they contain
arcuate nucleus - aggregation of neurons in medial basal area of hypothalamus (adjacent to 3rd ventricle) → has orexigenic neurons and anorectic neurons which project to paraventricular nucleus
paraventricular nucleus - contains neurons which project to posterior pituitary and secrete oxytocin and ADH from posterior pituitary
lateral hypothalamus - only contains orexigenic neurons
ventromedial hypothalamus - associated with satiety
define orexigenic
appetite stimulant
define anorectic
appetite suppressant
what do lesions in this area cause
why
ventromedial hypothalamus
lesions in rats cause obesity as the ventromedial hypothalamus is associated with inducing satiety
melanocortins here regulate feeding behaviour
debate about role in humans
how is the arcuate nucleus involved in appetite regulation
integrates central and peripheral feeding signals (from within and outside CNS) to coordinate an appropriate feeding response
contains orexigenic and norectic neurons which project into the paraventricular nucleus
the blood brain barrier is incomplete here → allows peripheral hormones in systemic circulation to access the arcuate nucleus
orexigenic neurons (stimulatory) → neuropeptide Y and AGRP neurons → increase food intake by releasing neuropeptide Y and by releasing AGRP which is a melanocortin receptor antagonist they are inhibited by leptin, insulin and peptide YY (stimulated by low insulin + leptin levels)
anorectic neurons (inhibitory) → POMC neurons → decrease food intake by releasing alpha-MSH they are stimulated by leptin and insulin and inhibited by NPY
what conditions would stimulate orexigenic neurons
why
conditions which decrease leptin and or insulin levels as leptin and insulin inhibit orexigenic neurons
diabetes, fasting, genetic leptin deficiency
label the neurons and stimulus and location
explain the role of the melanocortin system in feeding
central regulator of energy balance → involved in feeding behaviours + energy expenditure
melanocortin-4 receptors are expressed in paraventricular nucleus
when POMC neurons from arcuate nucleus are stimulated they release alpha-MSH (breakdown product of POMC) which binds to MC4 receptors
produces anorectic effect by triggering sensation of satiety
(AGRP/NPY neurons when stimulated release NPY → inhibits POMC and AGRP is MC4 receptor antagonist )
serotonin also upregulates alpha MSH
what does this graph suggest about the relationship about leptin levels between obese individuals and non obese individuals
serum leptin concentrations are significantly higher in obese than non-obese individuals
serum leptin concentration is positively correlated with body fat percentage → suggests that most obese people are insensitive to endogenous leptin
how can leptin levels be disrupted
what does this lead to
3 mechanisms:
decreased leptin secretion from adipose tissue → e.g. in ob/ob mice
disrupted receptor signalling → reduced leptin levels despite high adipose tissue mass
leptin resistance/decreased sensitivity → high levels of circulating leptin fail to cause satiety/reduce appetite (doesn’t signal effectively)
all lead to obesity
what is the role of ghrelin in appetite stimulation
how does it do this
ghrelin stimulates appetite and increases gastric emptying
ghrelin is highest pre-prandially → increases gastric motility, acid secretion + appetite → helps prepare for food intake
directly acts on neurons in the arcuate nucleus → stimulates orexigenic NPY/AGRP neurons + inhibits anorectic POMC neurons
ghrelin levels then decrease postprandially
this pre and post prandial changes in ghrelin suggest it has a role in initiating meals
ghrelin is als involved in reward regulation, taste sensation, memory and circadian rhythm
how would ghrelin levels vary over 24hrs
they would be highest pre-prandially (just before meals)
then decrease for around 1 hour post prandially (after meals)
interprandial (in between meals) ghrelin exhibits diurnal rhythm → increases until midnight/1am then decreases and reaches its lowest around 9am
what are the comorbidities of obesity
obesity affects the whole body
explain the meaning of this graph
there is interaction between genetics and the environment to cause obesity
in a healthy environment, amongst those who are genetically prone to obesity very few are obese, similar but slightly higher levels amongst those who are genetically resistant
however in a toxic environment obesity levels becomes much higher amongst those who are genetically prone compared to those who are resistant
obesity is increasing worldwide → higher prevalence of comorbidities → more hospital admissions
