What does appetite regulation entail?
Control of thirst Hypothalamic circuits controlling body weight Peripheral signals of body homeostasis - long term: leptin, short term: ghrelin, PYY
When does someone perceive thirst?
Body fluid osmolality is increased Blood volume is reduced Blood pressure is reduced Most potent is change of 2-3% of osmolality BUT 10-15% decrease is needed for same response from blood vol/arterial pressure
What does ADH/VP do?
Acts on kidneys to regulate volume and osmolarity of urine - when plasma ADH is low water diuresis occurs; when plasma ADH is high, antidiuresis occurs (small vol of urine)
Where are osmoreceptors found?
In the hypothalamus, organum vasculosum of the lamina terminalis, subfornical organ
What do the osmoreceptors do?
Sense changes in body fluid osmolality -> cells shrink/swell in response, sending signals to the ADH producing cells in the hypothalamus to alter ADH release
How is water balance maintained when there is increased plasma osmolality?
Invokes drinking and ADH release Increases ADH stimulating kidneys to conserve water
How is water balance maintained when there is decreased plasma osmolality?
Thirst is suppressed and ADH release is decreased Absence of aDH makes kidney excrete more water
How is thirst decreased and when is it decreased?
It can be decreased by drinking even before water has been absorbed by GIT to correct plasma levels. They relieve the sensation for a short time
When is thirst completely satisfied?
Once plasma osmolality is decreased or blood volume/arterial pressure is corrected
How is the renin-angiotensin-aldosterone system involved in the regulation of thirst?
AngII evokes sensation of thirst, increased when blood vol and pressure are reduced -> SFO neurons activated, contributing to the homeostatic response to restore/maintain body fluids at their normal level
How is body weight homeostasis maintained?
Ghrelin, PYY and other gut hormones, neural input from periphery and other brain regions and leptin are detected by the hypothalamus and then react to food intake and energy expenditure
What is the pathways with which skeletal muscle, pancreas, stomach, white adipose tissue and gut relay signals to higher centres?
What is the structure of the hypothalamus? FITB
What is the arcuate nucleus?
Key brain area involved in the regulation of food intake -> it has an incomplete blood brain barrier, allowing access to peripheral hormones Integrates peripheral and central feeding signals 2 neuronal populations: Stimulatory and inhibitory which are distinct from each other and regulated independently
Which is the stimulatory neuron in the arcuate nucleus?
Which is the inhibitory neuron in the arcuate nucleus?
How is appetite and energy expenditure controlled?
Cells bodies are in arcuate nucleus and axons extend to para ventricular nucleus
What is the melanocortin system?
Argp blocks signal from alpha MSH which causes hunger
Give 3 examples of types of human CNS mutations that affect appetite
No NPY/Agrp mutations associated with appetite discovered in humans POMC deficiency and MC4-R mutations can cause morbid obesity
What signals from other brain regions can affect appetite?
From higher centres Amygdala affects emotion and memory Other parts of the hypothalamus -> lateral hypothalamus Vagus to brainstem to hypothalamus
What is the adipostat mechanism?
Concentration of circulating hormone produced by fat is detected by hypothalamus which then alters neuropeptides to increase/decrease food intake
What is leptin?
Made by adipocytes in white adipose tissue, circulates in plasma and acts upon the hypothalamus regulating appetite and thermogenesis 167 a.a. hormone
How is the concentration of leptin different in different people?
Low when low body fat and high when high body fat
What does leptin do?
Decreases food intake and increases thermogenesis
What are the 3 possible ways the leptin regulatory loop can lead to obesity?
What is leptin resistance mechanism?
Leptin circulates in plasma in concentrations proportional to fat mass, so obesity due to leptin-resistance
What is congenital leptin deficiency?
Small number of cases identified -> mutation in ob gene, so person becomes severly hyperphagic and obese
How is congenital leptin deficiency treated?
Leptin replacement - which is effective in reducing body weight
What are the different enzymes secreted from the gut and their functions? FITB
What is the function of PYY?
Directly modulates neurons in the arcuate nucleus -> inhibits NPY release, stimulates POMC neurons and decreases appetite. Rises directly with amount of calories ingested
What is the function of ghrelin?
Directly modulates neurons in the arcuate nucleus -> stimulates NPY/Agrp neurons, inhibits POMC and increases appetite
What is the future of obesity treatment?
Gut hormones may represent a novel treatment for obesity, as it targets only relevant circuit, it's released daily without 'side effects' and exerts effect throughout life without escape
How is the brainstem triggered from the release of ghrelin and PYY? FITB
What comorbidities is obesity associated with?
Depression, stroke, sleep apnoea, myocardial infarction, hypertension, diabetes, bowel cancer, osteoarthritis, peripheral vascular disease, gout
What is the thrifty gene hypothesis?
In the past it was more sensible to be able to put on weight as the thin wouldn't survive famines, so obesity genes selected for
What are circumventricular organs?
They have an incomplete blood-brain barrier, so can sense changes in blood and respond to the changes. E.g. Organ vasculosum, subfornical organ
What receptors are involved in thirst detection?
Receptors in mouth, pharynx, oesophagus
What type of hormone is ghrelin?
Protein hormone with fatty acid chain (thought to help with passing the blood brain barrier)
What type of hormone is PYY?