1b Appetite Flashcards
What are the three things which stimulate thirst?
- Body fluid osmolality
- Blood Volume lowers
- Blood Pressure lowers
Which of the three stimuli for thirst is the most potent?
An INCREASE in plasma osmolality
Which hormone is the main regulator for osmolality?
ADH or Vasopressin
Where does ADH act?
Via the aqua porin 2 channel in the kidneys - renal collecting duct
When ADH is low, what volume of water is lost and what is this called?
Large volumes of urine is lost - diuresis
When ADH is high, what volume of water is lost and what is this called?
Small volume - anti-diuresis
Where is ADH stored
posterior pituitary gland
ADH is secreted through neurons in what region of the brain?
Hypothalamus
What regions are the sensory osmoreceptors found in the hypothalamus?
Organum vasculosum of the lamina terminalis (OVLT)
Subfornical Organ (SFO)
- Describe the process that leads to production of AVP and its subsequent function.
- When plasma is more concentrated, water moves out the osmoreceptors, causing them to SHRINK
- This means the PROPORTION OF CATION channels in the membrane increases
- This causes the membrane to depolarise
- Send signals to the ADH producing cells to increase ADH → Fluid retention, Invokes drinking
When is thirst completely satisfied?
Thirst is only completely satisfied once plasma osmolality is decreased or blood volume or arterial pressure corrected.
Which receptors are involved in the sensation of thirst?
Receptors in mouth, pharynx, oesophagus are involved - relief of thirst via these is short lived
What can excess excretion of water by kidneys lead to?
Waste of energy and can interfere with nutrient absorption which has a strong sodium dependence and is sodium driven
How does the renin-angiotensin system react to a decrease in blood pressure?
- Juxtaglomerular cells of renal afferent arteriole, once the decreased blood pressure here is detected, will release renin
- cleaves angiotensinogen in the liver to release angiotensin I
- Angiotensin I is converted into Angiotensin II in the lungs
- Angiotenin II Binds to receptors on the intraglomerular messenger cells
- This binding causes these cells to contract along with the blood vessels surrounding them, which then leads to release of aldosterone in the zona glomerulosa of the adrenal cortex
What are the three functions of angiotensin II?
Induces thirst - ADH secretion as well
Vasoconstriction, increase in sympathetic activity
Increase in enzyme activity of those involved in aldosterone release
How does aldosterone work in terms of water retention?
H20 retention via Na+Cl- absorption and K+ excretion
What 2 types of drugs that affect the RAAS are known to treat high blood pressure?
ACEi
Direct Renin Inhibitors
A reduction in body fat…
increases food intake and reduces energy expenditure
An expansion of adipose tissue…
reduces food intake and increases energy expenditure
In which state is there activation of the sympathetic nervous system?
Overfed state - adaptive physiological response used to stimulate thermogenesis and stabilise body weight during periods of over eating
How does reduced adipose tissue lead to weight regain?
Increased hunger and food intake
Decreased energy expenditure
Decreased sympathetic nervous system activity
Decreased thyroid function
How does increased adipose tissue lead to weight loss?
Decreased hunger and food intake
Increased energy expenditure
Increased sympathetic nervous system activity
Leads to weight loss
What is the significant hormone involved in the central circuit defense against reduction of body fat?
Leptin
Where does the most important regulation of appetite occur?
Hypothalamus
What are the two main gut hormones involved in the regulation of appetite?
GHRELIN, PYY & other gut hormones
Which nerve do signals from Ghrelin and PYY travel to the brainstem via?
Vagus nerve
Other than the gut hormones through vagus nerve, how else does the hypothalamus receive input about appetite regulation?
Neural input from the periphery and other brain regions
Leptin
What is the part of the hyopthalamus which is an aggregation of neurones in the medial basal part and it is the most important site in hypothalamic integration of energy balance called?
Arcuate nucleus
What is the name of the nucleus in the hypothalamus that has neurons projecting to the posterior pituitary?
Paraventricular nucleus
What is meant by orexigenic?
Appetite Stimulant
What term is used to describe an appetite suppressor?
Anorectic
how does the arcuate nucleus allow access to peripheral hormones?
Incomplete blood brain barrier
Where are orexigenic peptides produced?
The lateral hypothalamus
What is the ventromedial hypothalamus involved with?
Satiety - the feeling of being full
where in the hypothalamus are melanocortins found?
Ventromedial hypothalamus
Which neurones form part of the stimulatory system in the arcuate nucleus?
NPY/AGRP neuron
Which neurones form part of the inhibitory system in the arcuate nucleus?
POMC neurone
Which mutations cause morbid obesity in humans?
POMC deficiency and MC4-R mutations cause morbid obesity.
What effect does the amygdala have on appetite?
Plays a strong role in the reward-motivation pathways in the brain
Regulating appetite with response to emotions
How does the adipostat mechanism work?
Circulating hormones (can be leptin) are produced by adipose tissue
The more adipose tissue → the more hormones being produced
Hypothalamus senses the concentration of hormone
Hypothalamus uses this to alter neuropeptides to increase or decrease food intake
What effect does leptin have on maintaining body temperature and therefore expenditure?
Leptin increases thermogenesis
Thermogenesis is the dissipation of energy through production of heat and occurs in brown adipose tissue and skeletal muscle
This therefore increases energy expenditure
Where is leptin produced?
adipocytes in white adipose tissue and enterocytes
What are the level of leptin when the body fat is low and high?
Low when low, high when high
What is given to children with congenital leptin deficiency?
leptin has been effective in reducing body weight.
Describe how leptin resistance can arise?
Fat humans have high leptin levels
However leptin might not signal correctly
Therefore leptin will not be an effective weight control drug
What are the gastrointestinal hormones that regulate appetite released by?
Secreted by enteroendocrine cells in the stomach, pancreas & SB
What are the two gut hormones which control appetite?
Ghrelin and PYY
What is the overall function of ghrelin?
Stimulates appetite, increases gastric
emptying
What are the functions of ghrelin in the gastrointestinal tract?
Increase gastric motility
Increase acid secretion
how does ghrelin affect appetite?
Directly modulates neurons in the arcuate nucleus to increase appetite
Stimulates NPY/Agrp neurons
Inhibits POMC neurons
When are levels of ghrelin highest in the body?
Before a meal
other than appetite what does ghrelin regulate?
Regulation of reward, taste sensation, memory, circadian rhythm
What method is used to measure the levels of ghrelin throughout the day?
Radioimmunoassay
What is the rhythm of ghrelin release?
Diurnal
Rising throughout the day to highest at 1am
Lowest at 9am
What is PYY?
Peptide tyrosine tyrosine
Where is PYY released?
Short peptide released in the terminal ileum (TI) and colon in response to feeding (36 Amino acids)
what effect does PYY have on appetite?
Reduced appetite
How does PYY reduce appetite?
- Food arriving to the TI and colon results in PYY release
- Inhibits NPY release
- Stimulates POMC neurons
What types of foods initiates the best PYY response?
Dietary fibres, wholegrains, and enzymatic breakdown of crude fish proteins
Degree of release of PYY is proportional to what variable?
Caloric intake
What are some of the side effects of PYY?
Nausea, fullness especially with higher dose
Less hunger and early fullness in the premeal period during PYY infusions
What are some of the comorbidities with obesity?
Stroke
MI
Hypertension
Diabetes
Peripheral vascular disease
Gout
OA
Bowel cancer
Sleep apnoea
Depression
Other than bowel cancer, what other cancer is suspected of being related to obesity?
Breast
What 2 categories of risk factors lead to an increase in obesity?
Genetic and environmental
What would the concentrations in the arcuate nucleus be of the 2 neuron populations if there was a need to stimulate food intake?
Increasing Neuropeptide Y signalling
Reducing melanocortin signalling via release of AGRP (endogenous melanocortin receptor antagonist
Describe how appetite and energy expenditure is controlled from the blood?
Circulating factors in the blood
NPY/Agrp released from arcuate to paraventricular nucleus to increase feeding
What receptors for alpha MSH are expressed in the paraventricular nucleus of the hypothalamus?
MC4R
What effect does AGRP have on MC4 receptor?
It is a competitive antagonist
Describe how hunger is controlled using the two neuronal populations in the arcuate nucleus?
hunger:
- Ghrelin activates NPY/AgRP neurones and inhibit POMC neurones in the ARC
- This results in the inhibition of anorectic neurones in the PVN which suppress the feeling of hunger, leading to hunger and hence an increase in foo intake
Ghrelin directly modulates neurones in which brain area?
Arcuate nucleus
