15 Appetite Flashcards
Q: 3 forms of appetite regulation.
A: The control of thirst Hypothalamic circuits controlling body weight Peripheral signals of body homeostasis Long Term- Leptin Short term – Ghrelin, PYY
Q: When does an individual perceive thirst? (3) What induces a strong desire to drink? (2)
A: Body fluid osmolality is increased.
Blood volume is reduced.
Blood pressure is reduced.
Plasma osmolality increased is the more potent stimulus – change of 2-3%
would need same response with decrease of 10-15% in blood volume or arterial pressure
Q: What are the 2 key organs involved in water regulation? Actions? (3) What is tightly regulated? why? (3) how?
A: gut and kidney
absorption, reabsorption and excretion
osmolality (concentration) of blood is very tightly regulated (285-295 mOsm/kg) to maintain solute gradients, a suitable haematocrit and the ideal viscosity.
kidneys can produce urine of wildly different osmolalities (50-1200 mOsm/kg).
Q: What can sense change in solute concentration? Smaller sensor?
A: osmoreceptors in the brain adjacent to structures with an incomplete blood brain barrier.
Principally the hypothalamus, within the OVLT and SFO regions.
During (even mild) dehydration, the hypothalamic response is considerably more sensitive than peripheral baroreceptors (which respond to changes in blood volume and pressure).
Q: Where is vasopressin produced? goes to? What are its primary functions? (2) Similar to? aim? Minor action?
A: Vasopressin (antidiuretic hormone; ADH) = hormone
in the hypothalamus and released from the posterior pituitary gland.
Its primary functions are:
- insert aquaporin-2 channels into the collecting duct of renal nephrons to increase water reabsorption
- stimulate vasoconstriction
These mechanisms (in a similar way to angiotensin II) combine to conserve blood volume and to increase blood pressure.
Beyond stimulating water retention, they stimulate THIRST to increase behaviours that will lead to increased fluid intake.
Q: Describe urine produced when we have high ADH production. Low. What are they both called?
A: 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)
Q: What is diuresis?
A: increased or excessive production of urine
Q: What regulates the production of ADH? Describe the location of this structure. (4) 3 examples.
A: Osmoreceptive cells
- in the brain -> have
- cell bodies outside of the blood brain barrier that are
- bathed in the extracellular fluid (ECF)
- ie adjacent to structures with an incomplete blood brain barrier.
Principally the hypothalamus, within the OVLT and SFO regions (Circumventricular organs)
Q: 3 step process to how osmoreceptors regulate ADH production. What does increased ADH lead to? (2)
A: 1. These cells are very sensitive to their local environment and quickly equilibrate with it.
- If the ECF varies from about 290 mOsm/kg, the cells will proportionately grow (in response to reduced osmolality) or shrink (in response to increased osmolality) by osmosis.
- These changes will affect the firing rate of these cells, which will adjust the basal level of ADH being secreted.
Increased ADH secretion will lead to water retention (and a decreased osmolality).
Q: What does increased plasma osmolarity invoke? (2) result?
A: Invokes drinking and ADH release
Increased ADH stimulates kidney to conserve water
Q: What does decreased plasma osmolarity invoke? (2) result?
A: Thirst is suppressed and ADH release decreased
Absence of ADH the kidney excretes more water
Q: What are the 2 ways thirst can be satiated (satisfied, quenched)? Which is short term? long term? Mechanism? (2)
A: the presence of water in the GI tract can quench thirst, for a short period of time at least. This is thought to results from receptors in the upper GI tract (mouth to oesophagus) - short term feedback
once the original stimulus (osmolality or blood pressure) has been corrected, then the perception of thirst is no longer felt - long term feedback
Q: What are the 6 functions of angiotensin II?
A: 1. It binds to receptors on vascular smooth muscle cells to stimulate vasoconstriction
- It upregulates activity of the sympathetic nervous system, which largely promotes vasoconstriction
- It stimulates aldosterone secretion, which increases sodium reabsorption in the nephron, which creates an osmotic gradient for water reabsorption
- It directly influences sodium reabsorption, causing water reabsorption
- It stimulates ADH release and stimulates thirst
- Activates SFO neurons
Q: When is ANG II released? 3 needed components to make?
A: when blood volume and pressure are reduced.
- juxtaglomerular cells of renal afferent arteriole make renin
- liver makes angiotensinogen
- cleaving-> ANG I
- Angiotensin converting E (expressed on the vascular endothelial cells of the pulmonary and renal microvessels) -> ANG II
Q: What structure is responsible for body weight homeostasis? 3 inputs. 2 outputs.
A: hypothalamus
inputs from periphery:
- hormones: GHRELIN, PYY & other gut hormones
- Neural input from the periphery and other brain regions
- leptin
- control of food intake
- control of energy expenditure
Q: What is the organisation of the hypothalamus? In relation to appetite regulation, what is key?
A: complex arrangement of nuclei and neurons
arcuate nucleus
paraventricular nucleus
Q: Where is the arcuate nucleus? What does it have? allows? What are the 2 neuronal populations it contains?
A: part of hypothalamus located at the base of the brain
has an incomplete blood brain barrier, which allows peripheral signals (nutrients, hormones, concentrations, temperature etc.) to directly activate its circuitry
- NPY/Agrp (Neuropeptide Y/Agouti-related peptide)
o located medially
o NPY/Agrp neurons STIMULATE food intake (and appetite) - POMC (proopiomelanocortin)
o located more laterally.
o POMC neurons INHIBIT food intake (and appetite)
Q: What is POMC? can be?
A: POMC = long peptide that can be cleaved many ways for many different purposes
Q: What’s the link between the paraventricular nucleus and arcuate? Other inputs? (4)
A: - both nuclei in hypothalamus
- axons from POMC and NPY/Agrp neurons in arcuate nucleus can project to (lots of locations in brain inc.) paraventricular nucleus
- neuropeptides are released to bind to receptors in paraventricular nuclei
Higher centres.
Amygdala- emotion, memory.
Other parts of the hypothalamus (lateral hypothalamus) -> could be linked to reward
Vagus to brain stem to hypothalamus.
Q: Draw a diagram of the hypothalamus including 5+1 other structures.
A: REFER
Q: Describe the actions of the POMC neuronal population. (5) Mutations? (2)
A: 1. axons from POMC neurons in arcuate nucleus project to paraventricular nucleus
- alpha MSH (satieting signal (i.e. I’m full and I don’t need to eat)) is made from POMC -> released (firing rate can be altered by circulating factors crossing blood brain barrier)
- binds to MC4R (melanocortin 4R) receptor
- agonising it (potentiates/combines with the cell receptor to produce some reaction that is typical for that substance)
- causing reduction in food intake
POMC deficiency and MC4R mutation is known to cause morbid obesity
Q: Describe the actions of the NPY/Agrp neuronal population. (5) Mutations?
A: 1. axons from NPY/Agrp neurons in arcuate nucleus project to paraventricular nucleus
- Agrp -> released (firing rate can be altered by circulating factors crossing blood brain barrier)
- binds to MC4R (melanocortin 4R) receptor
- antagonising it
Q: What is the appetite regulating system called? Explain.
A: melanocortin
Agrp and alpha MSH (from POMC) from arcuate nucleus binding to receptors in paraventricular nucleus -> melanocortin 4 receptor (MC4R) where activation (by alpha MSH) decreasing food intake
Q: Name 3 peripheral signals of body (weight) homeostasis. Split.
A: Long Term- Leptin
Short term – Ghrelin, PYY
Q: What is leptin? provides? What secretes it? Function? (3)
A: hormone (circulates in blood)
provides long term appetite regulation
cells in white adipose tissue
binds to receptors in the hypothalamic circuits and stimulates anorexigenic behaviours (i.e. suppresses appetite) and regulates thermogenesis (expenditure).
Q: What is the evolutionary premise of leptin?
A: a well-nourished adult will accumulate body fat, which in turn increases leptin secretion and suppressing appetite. However, this feedback mechanism can become dysfunctional, as leptin resistance is associated with obesity.
Q: What’s the adipostat mechanism?
A: 1. 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 ?
Q: Draw a pathway for leptin action. (7)
A: adipose tissue
-> makes leptin ->
goes to hypothalamus
3 things affected
- food intake (decreases)
- energy expenditure (increases)
- fat and glucose metabolism
Q: Identify 3 ways the leptin regularity loop could lead to obesity. What did studies reveal? (2) Can leptin cure obesity?
A: 1. absent obesity
- regularity defect (normal leptin levels) you may put on more fat but leptin doesn’t go up accordingly
- leptin resistance (high levels of it) hypothalamus is not signalling properly
- 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
Q: What can congenital leptin deficiency cause? (2) What helps? Common?
A: Severely hyperphagic = an abnormally great desire for food
obese
leptin is an effective form of weight control (help them lose)
RARE
Q: Why do we feel less hungry after a meal?
A: hormonal signalling from gut
Q: What is PYY? Where is it secreted? When?
A: PYY3-36 is a peptide hormone that regulates short-term appetite control: ‘satiety hormone’
secreted from cells in the ileum and colon in response to a meal (proportional to calory intake)
Q: What does PYY do? 3 outcomes.
A: PYY3-36 directly modulates neurons in the arcuate nucleus (binds to hypothalamic receptors)
- Inhibits NPY release.
- Stimulates POMC neurons.
- Decreases appetite.
Q: What is ghrelin? Secreted from? amount?
A: Ghrelin is a peptide hormone that regulates short-term appetite control by promoting eating behaviours= ‘hunger hormone’
secreted from cells in the stomach in increasingly higher quantities in the build up to a meal
Q: What does ghrelin do? 3 outcomes.
A: directly modulates neurons in the arcuate nucleus (binds to hypothalamic receptors)
- Stimulates NPY/Agrp neurons.
- Inhibits POMC neurons.
- Increases appetite
Q: Name 4 co morbidities associated with obesity.
A: diabetes
gout
hypertension
myocardial infarction
