Appetite

Question 1

Control of thirst

Answer 1

Body fluid osmolarity
Reduced blood volume
Reduced blood pressure

Question 2

Most potent thirst stimulus

Answer 2

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

Question 3

Hormone for regulation of osmolarity

Answer 3

Antidiuretic hormone or vasopressin

Question 4

ADH action

Answer 4

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)

Question 5

Osmoreceptors

Answer 5

Sensory receptors

Osmoregulation

Question 6

Osmoreceptor location

Answer 6

Hypothalamus

In organum vasculosum of lamina terminalis (OVLT) and subfornical organ (SFO)

Question 7

Osmoreceptor responses

Answer 7

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

Question 8

Sensation of thirst

Answer 8

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

Question 9

Change in blood pressure and thirst

Answer 9

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

Question 10

Angiotensin II effects

Answer 10

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

Question 11

Peripheral signalling for appetite regulation

Answer 11

Ghrelin and PYY
Travels through vagus, connects to brain stem, then communicates with hypothalamus

Also leptin

Question 12

Arcuate nucleus

Answer 12

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

Question 13

Paraventrivular nucleus

Answer 13

Of hypothalamus

Next to third ventricle

Contain neurons that project to posterior pituitary where ADH is stored

Neurons secrete oxytocin and ADH

Question 14

Lateral hypothalamus

Answer 14

Only produce orexigenic peptides

Question 15

Ventromedial hypothalamus

Answer 15

Associated with satiety

Lesions lead to severe obesity

Question 16

Melanocortin system

Answer 16

Arcuate nucleus - alpha MSH (stimulate MC4R) or Agrp (inhibit MC4R) secreted
Paraventricular nucleus - melanocortin-4 receptors expressed stimulated by serotonin and decreases food intake

Question 17

Human CNS mutations affecting appetite

Answer 17

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

Question 18

Signals from other brain regions

Answer 18

Higher centres

Amygdala - emotion, memory
Other parts of hypothalamus - lateral and ventromedial hypothalamus
Vagus to brainstem to hypothalamus

Question 19

Adipostat mechanism

Answer 19

Circulating hormone produced by fat
Hypothalamus senses concentration of hormone
Hypothalamus alters neuropeptides to increase or decrease food intake

Question 20

Leptin

Answer 20

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

Question 21

Congenital leptin deficiency

Answer 21

Rare condition
Born with normal weight but constantly hungry
Results in obesity
Intake of leptin help reduce body weight

Question 22

Leptin systemic effects

Answer 22

Low when low body fat
High when high body fat
Hormone that decreases food intake and increases thermogenesis

Question 23

Leptin mechanism of action

Answer 23

Absent leptin
Regulatory defect - signalling - reduced leptin despite high adipocyte tissue mass
Leptin resistance

Question 24

GI hormones

Answer 24

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

Question 25

Ghrelin

Answer 25

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

Question 26

Peptide tyrosine tyrosine

Answer 26

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

Question 27

Environmental and genetic influences on obesity

Answer 27

Genetically prone and toxic environment most at risk

Genetically resistant are fine in healthy or toxic environments