Appetite Flashcards
Control of thirst
Body fluid osmolarity
Reduced blood volume
Reduced blood pressure
Most potent thirst stimulus
Plasma osmolarity increase - change of 2-3% induces strong desire to drink
Decrease of 10-15% in blood volume of arterial pressure required to produce same effect
Hormone for regulation of osmolarity
Antidiuretic hormone or vasopressin
ADH action
Acts on kidney to regulate volume and osmolarity of urine
- collecting duct - aquaporin 2 channel
Low plasma ADH - large volume of urine excreted (water diuresis)
High plasma ADH - small volume of urine excreted (anti diuresis)
Osmoreceptors
Sensory receptors
Osmoregulation
Osmoreceptor location
Hypothalamus
In organum vasculosum of lamina terminalis (OVLT) and subfornical organ (SFO)
Osmoreceptor responses
Cells shrink when plasma is more concentrated
Proportion of cation channels increases - membrane depolarises increasing firing frequency
Send signals to ADH producing cells to increase ADH
Fluid retention invokes drinking
Sensation of thirst
Thirst decreased by drinking before sufficient water has been absorbed by GI tract to correct plasma osmolarity
Receptors in mouth, pharynx, oesophagus involved
Relief of thirst through these receptors is short-lived
Thirst only completely satisfied once plasma osmolarity is decreased or blood volume or arterial pressure corrected
Change in blood pressure and thirst
Decreased BP
Juxtaglomerular apparatus secrete renin (angiotensinogenase) from kidneys
Renin cleaves angiotensinogen secreted by liver which becomes angiotensin I
Angiotensin I converted to II through angiotensin converting enzymes in lungs
Angiotensin II effects
Induces thirst
ADH secretion
Activates sympathetic system leading to vasoconstriction
Binds to intraglomerular messenger cells causing cells to contract along with blood vessels surrounding them
Release of aldosterone in zona glomerulosa of adrenal cortex
Aldosterone influences reabsorption of sodium and excretion of potassium, and influences water retention
Also regulates BP, plasma sodium and plasma potassium
Peripheral signalling for appetite regulation
Ghrelin and PYY
Travels through vagus, connects to brain stem, then communicates with hypothalamus
Also leptin
Arcuate nucleus
Of hypothalamus
Medial basal part
Incomplete blood brain barrier - allows access to peripheral hormones through circulating factors in blood
Produces appetite increasing (orexigenic) - NPY and Agrp and appetite decreasing (anorectic) - POMC neurons
Next to third ventricle
Send signals through third ventricle to paraventricular nucleus
Paraventrivular nucleus
Of hypothalamus
Next to third ventricle
Contain neurons that project to posterior pituitary where ADH is stored
Neurons secrete oxytocin and ADH
Lateral hypothalamus
Only produce orexigenic peptides
Ventromedial hypothalamus
Associated with satiety
Lesions lead to severe obesity
Melanocortin system
Arcuate nucleus - alpha MSH (stimulate MC4R) or Agrp (inhibit MC4R) secreted
Paraventricular nucleus - melanocortin-4 receptors expressed stimulated by serotonin and decreases food intake
Human CNS mutations affecting appetite
No NPY or Agrp mutations associated with appetite in humans
POMC deficiency and MC4R mutations cause morbid obesity
Mutations not responsible for prevalence of obesity but useful to explain signalling
Signals from other brain regions
Higher centres
Amygdala - emotion, memory
Other parts of hypothalamus - lateral and ventromedial hypothalamus
Vagus to brainstem to hypothalamus
Adipostat mechanism
Circulating hormone produced by fat
Hypothalamus senses concentration of hormone
Hypothalamus alters neuropeptides to increase or decrease food intake
Leptin
Made by adipocytes in white adipose tissue and enter oxygen
Circulates in plasma
Acts upon hypothalamus regulating appetite (intake) and thermogenesis (outtake)
Ineffective as weight loss drug
Congenital leptin deficiency
Rare condition
Born with normal weight but constantly hungry
Results in obesity
Intake of leptin help reduce body weight
Leptin systemic effects
Low when low body fat
High when high body fat
Hormone that decreases food intake and increases thermogenesis
Leptin mechanism of action
Absent leptin
Regulatory defect - signalling - reduced leptin despite high adipocyte tissue mass
Leptin resistance
GI hormones
Secreted by enteroendocrine cells in stomach, pancreas abd small bowel
Appetite regulated by
Ghrelin - stimulate appetite, increase gastric emptying
Peptid YY (PYY) - inhibits food intake
Ghrelin
Blood levels highest before meals
Help prep for food intake by increasing gastric motility, acid secretion and appetite
Directly modulated neurons in arcuate nucleus - stimulate NPY/Agrp and inhibit POMC
Regulation of reward, taste sensation, memory, circadian rhythm
Peptide tyrosine tyrosine
Short peptide released in terminal ileum and colon in response to feeding
Reduces appetite - can be digested or injected IV
Food arriving to TI and colon results in release
Inhibits NPY release
Stimulates POMC neurons
Environmental and genetic influences on obesity
Genetically prone and toxic environment most at risk
Genetically resistant are fine in healthy or toxic environments
