Appetite Flashcards
What are the 3 main triggers of the control of thirst?
- plasma osmolality
- reduced blood volume
- reduced blood pressure
What is the most potent stimulus for thirst control?
Plasma osmolality
What change in plasma osmolality is required to induce thirst?
2-3%
What change in blood volume/arterial pressure is required to induce thirst?
10-15%
How does the body regulate osmolality?
Anti-diuretic hormone (ADH)/vasopressin
Where does ADH act?
- on the kidneys to regulate the volume and osmolality of urine
- collecting duct, V2 receptor
What happens when ADH is low?
large volumes of urine is excreted (water diuresis)
What happens when ADH is high?
small volumes of urine are excreted (anti-diuresis)
Where is ADH stored?
in the posterior pituitary gland
How does the body measure osmolality?
via osmoreceptors in the hypothalamus
What are osmoreceptors? DELETE
- sensory receptors
- involved in osmoregulation
- found in the hypothalamus
Where are osmoreceptors in the hypothalamus?
- Organum vasculosum of the lamina terminalis (OVLT)
- Subfornical Organ (SFO)
How is ADH release regulated in a dehydrated condition?
- cells shrink when plasma is more concentrated
- the proportion of cation channels increases, and the membrane depolarizes
- sends signals to ADH producing cells to increase ADH
- fluid retention, invokes drinking
How is ADH release regulated in a hydrated condition?
- cells expand when plasma is less concentrated
- cation channels are inhibited, the membrane is hyperpolarised
- inhibits signals
- excretion of fluid
What causes a decrease in thirst?
drinking
What detects that drinking has occured in order to stop thirst?
receptors in the mouth, pharynx and oesophagus
When is thirst completely satisfied?
when plasma osmolality is decreased or blood volume/arterial pressure is corrected
What type of relief is provided by mouth/pharynx/oesophagus receptors?
temporary
What else can prompt thirst?
- habit
- cravings
- desire
What are the negatives of excessive fluid consumption?
- energy wastage
- decreased plasma osmolarity
- interference with nutrient absorption (dependent/driven by sodium)
What system responds to changes in blood pressure/volume?
the renin-angiotensin-aldosterone system
What happens when blood pressure drops?
juxtaglomerular apparatus secretes renin
Where is the juxtaglomerular apparatus?
The hilus of the glomerulus
What happens when renin is released?
activates the renin-angiotensin system by cleaving angiotensinogen into angiotensin I
What secretes angiotensinogen?
the liver
What happens to angiotensin I?
it is converted into angiotensin II by (angiotensin converting enzyme) in the lungs
What is the effects of angiotensin II?
- induces thirst
- release of aldosterone
- ADH secretion
- vasoconstriction (increased sympathetic activation)
What does aldosterone do?
Influences: - sodium reabsorption - potassium excretion and therefore, - water retention
What happens when there is a reduction in fat mass?
- increase in food intake
- reduction in energy expenditure
- reduces the effect of the thyroid gland
- sympathetic inhibition
What happens when there is adipose tissue expansion?
- reduces food intake
- increases energy expenditure
- sympathetic activation
What is the impact of changes in adipose tissue?
activates responses that favour the return to the previous/original weight
Which part of the brain regulates hunger?
hypothalamus
What are the 2 main gut hormones involved in appetite regulation (peripheral signalling)?
- Ghrelin
- PYY
What is the long term hormonal appetite regulation?
leptin system
What are the 3 main factors involved in appetite regulation?
- Ghrelin/PYY
- neural input from periphery/other brain regions
- Leptin
What does orexigenic mean?
appetite stimulant
What does anorectic mean?
appetite supressive
What is the role of the arcuate nucleus?
- regulation of food intake
- both orexigenic and anorectic
- integrates peripheral and central feeding signals
How does the arcuate nucleus allow access to peripheral hormones?
Incomplete blood-brain barrier
What are the two neuronal populations of the arcuate nucleus?
- stimulatory NPY/AGRP neuron
- inhibitory POMC neuron
What is the role of the paraventricular nucleus?
- neurones to the posterior pituitary (oxytocin)
- regulates appetite
What is the role of the lateral hypothalamus?
produces orexigenic peptides
What is the role of the ventromedial hypothalamus?
satiety
What is the effect of lesions in the ventromedial hypothalamus?
severe obesity
What is the effect of arcuate nucleus pro-opiomelanocortin (POMC) neurones?
reduced food intake
What is also thought to be implicated in appetite regulation?
- endocannabinoids
- AMP (activated protein kinase)
- protein tyrosine phosphokinase
Where are NPY/Agrp neurones found?
only in the arcuate nucleus
How do NPY/Agrp neurones stimulate food intake?
make peptides that:
- increase NPY signaling
- reducing melanocortin signaling
by AGRP release
What is ARGP?
an endogenous melanocortin receptor antagonist
What can activate NPY/Agrp neurones?
decrease in:
- leptin
- insulin
What conditions cause an increase in food intake by impacting the NPY/Agrp neurones?
- fasting
- uncontrolled diabetes
- genetic leptin deficiency
What is the arcuate nucleus involved in?
- feeding
- fertility
- cardiovascular regulation
What is in the central melanocortin system?
- NPY
- AGRP neurones
- POMC
What are melanocortins?
products of the POMC
What is an example of melanocortin
alpha-MSH
What is the role of the central melanocortin system?
central regulator of energy balance
including:
- feeding behaviours
- energy expenditure
Where are melanocortin-4 receptors expressed?
paraventricular nucleus
What stimulates melanocortin-4 receptors?
serotonin
What is the effect of the stimulation of melanocortin-4 receptors?
- reduction of appetite
- weight loss
- reduced food intake
What has a encouraging/stimulating effect on melanocortin-4 receptor?
alpha-MSH
What has a inhibiting effect on melanocortin-4 receptor?
Agrp
What is the effect of Agrp and NPY mutations?
No associated effects to appetite
What is the effect of POMC deficiency and MC4-R mutations?
causes morbid obesity
What role does the amygdala play?
controls reward related motivation pathways, affects appetite
How is neural information from the digestive tract passed on to the hypothalamus?
carried by the vagus to the brain stem and eventually the hypothalamus
What is the adipostat mechanism?
- circulating hormones are produced by adipose tissue (more=more hormone)
- concentration sensed by the hypothalamus
- hypothalamus alters neuropeptides to change food intake
What produces leptin?
- adipocytes in white adipose tissue
- enterocytes
What does leptin do?
- acts on the hypothalamus
- decreases appetite (intake)
- increases thermogenesis (expenditure)
When is leptin low or high?
- low when low body fat
- high when high body fat
Where in the hypothalamus does leptin act?
- arcuate nuclei
- ventromedial nuclei
What is the role of leptin?
- regulation of adipose tissue mass
- development of atherosclerosis (innate system)
What conditions have been associated with low levels of leptin?
- Alzheimer’s disease
- Depression
What happens in congenital leptin deficiency?
RARE
morbid/severe obesity
low serum leptin levels
How can congenital leptin deficiency be managed?
leptin replacement to reduce body weight
What happens to serum leptin in obesity?
- serum leptin concentration is correlated to the body fat %
- obesity due to leptin resistance
What are the mechanisms of leptin in obesity?
- absent leptin
- leptin resistance
- regulatory defect in leptin (signalling issue)
Would leptin be an effective weight control drug?
No, due to leptin resistance
What reduces hunger after a meal?
hormonal signalling from the gut
What secretes gut hormones?
enteroendocrine cells in:
- stomach
- pancreas
- small intestine
What are the roles of the gut hormones?
- motility regulation
- appetite regulation
- satiety
- salivation
What is the effect of Ghrelin?
- stimualtes appetite
- increases gastric emptying
What is the effect of Peptide YY?
inhibits food intake
When is Ghrelin highest?
- before meals
- increases gastric motility and acid secretion
- prepares for food intake
What impact does Ghrelin have in the hypothalamus?
- stimulates NPY/Agrp neurones
- inhibits POMC neurones
What does Ghrelin regulate?
- reward
- taste sensation
- memory
- circadian rhythm
- increases appetite
What rhythm is seen by Ghrelin levels?
diurnal rhythm
What does circulating Ghrelin correlate with?
- time of day
- positive with age
What is the physiological role of Ghrelin?
meal initiation
Where is Peptide tyrosine tyrosine (PYY) released?
- terminal ileum and colon
- response to feeding
What is the effect of PYY in the hypothalamus?
- stimulates POMC neurones
- inhibits NPY release
What types of food trigger PYY release?
- dietary fibres
- wholegrains
- enzymatic breakdown of crude fish proteins
What does PYY do?
induces satiety/reduces appetite
What is the degree of PYY release proportional to?
calorie intake
What are the side effects of PYY?
- nausea
- fullness
- less hunger
- early fullness
What co-morbidities are associated with obesity?
- depression
- stroke
- sleep apnoea
- MI
- hypertension
- diabetes
- bowel cancer
- osteoarthritis
- peripheral vascular disease
- gout
Which factors are most dominant in terms of increasing risk of obesity?
environmental factors and genetic predisposition
