12. Regulation of appetite

Question 1

State three triggers of thirst. Which is most potent?

Answer 1

Increase in plasma osmolality (most potent)
Decrease in blood volume
Decrease in BP

Question 2

Where are the osmoreceptors that trigger ADH release located?

Answer 2

OVLT: organum vasculosum
SFO: subfornical organ
Hypothalamus

Question 3

Urine excretion when plasma ADH is high and low

Answer 3

High: Small volume of urine excreted
Low: Large volume of urine excreted

Question 4

How do the circumventricular organs detect changes in plasma osmolality?

Answer 4

Have an incomplete blood brain barrier (BBB) so they can detect the changes taking place in the periphery, they are NOT isolated by the BBB.
Changes in plasma osmolality make the cells shrink or swell which signals to the ADH producing cells in the hypothalamus to change ADH release.

Question 5

How come thirst is temporarily relieved when you drink water but before it has any effect on plasma osmolality?

Answer 5

Receptors in the mouth, pharynx and oesophagus that are involved in this temporary relief of thirst.

Question 6

What happens at increased and decreased plasma osmolarity?

Answer 6

Increased: Invokes drinking and ADH release (stimulates kidney to conserve water)
Decreased: Thirst suppressed and ADH release decreased (kidney excretes more water)

Question 7

When is thirst completely satisfied?

Answer 7

When plasma osmolarity is decreased or blood volume/ pressure are corrected

Question 8

What major hormone is involved in regulating thirst? What does it do?

Answer 8

Angiotensin II
Stimulates fluid retention
Stimulates thirst
Causes vasoconstriction and release of aldosterone

Question 9

What neural and hormonal components have an effect on the hypothalamus in regulating food intake and energy expenditure?

Answer 9

Neural: Vagal afferents
Hormonal: Ghrelin, PYY, Leptin

Question 10

Which part of the brain is heavily involved in regulating hunger and what does it communicate with?

Answer 10

Arcuate nucleus

Located beneath the 3rd ventricle and communicates with the paraventricular nucleus (above the 3rd ventricle)

Question 11

What are the 2 groups of neuronal populations in the arcuate nucleus and what effect does this have on hunger?

Answer 11

Stimulatory: NPY/Agrp
Inhibitory: POMC

Question 12

What feature of the arcuate nucleus makes this good for regulating hunger?

Answer 12

It’s a circumventricular organ
Has an incomplete BBB thus allowing access to peripheral hormones.
It integrates peripheral and central feeding controls.

Question 13

Describe the melanocortin system and how it regulates hunger.

Answer 13

POMC cleaved to produce alpha-MSH, stimulates melanocortin-4 receptor (MC4R) and suppresses food intake.
Agrp, acts as an endogenous antagonist on MC4R, blocks inhibitory signal from MC4R, makes you feel hungry.

Question 14

What mutations or deficiencies within this system can cause obesity?

Answer 14

MC4R deficiency

POMC mutation

Question 15

What other regions of the brain are involved in regulating appetite?

Answer 15

Higher centres
Amygdala (emotion, memory)
Other parts of the hypothalamus
Vagus to brain stem to hypothalamus

Question 16

Where is leptin produced and what does it allow the regulation of?

Answer 16

Produced by adipocytes in white adipose tissue.
Circulates in plasma
Hypothalamus senses the concentration of leptin, then alters neuropeptides to regulate appetite and thermogenesis

Question 17

When is leptin low and high?

Answer 17

Low: Low body fat
High: High body fat

Question 18

Main effects of leptin

Answer 18

Decrease food intake

Increase thermogenesis

Question 19

State 3 possible mechanisms that would make leptin responsible for obesity.

Answer 19

Absence of leptin
Regulatory defect: Inability of leptin stores to increase proportionally with increasing fat
Leptin resistance

Question 20

What is the association between leptin and obesity?

Answer 20

Obesity is due to leptin resistance
leptin is present but doesn’t signal effectively
Thus leptin is ineffective as a weight control drug

Question 21

What condition can leptin be used therapeutically for?

Answer 21

Congenital leptin deficiency

severally hyperphagic and obese

Question 22

What determines the amount of PYY secreted?

Answer 22

The size of the meal (calories)

Question 23

Structure of PYY

Answer 23

36 AA chain

If the first 2 AA’s are cleaved after a meal, forms Pyy3-36, appetite is suppressed

Question 24

What effects does PYY3-36 have on the arcuate nucleus?

Answer 24

Inhibits NPY release
Stimulates POMC neurons
Decreases appetite

Question 25

What structure in Ghrelin is necessary for its receptor activity?

Answer 25

Fatty acid on the 3rd AA position which is required for receptor activity and it helps it to slip across membranes.

Question 26

Describe the action of Ghrelin on the neurones of the arcuate nucleus

Answer 26

Ghrelin has the opposite action to PYY.
Stimulates NPY/Agrp neurones
Inhibits POMC
Increases appetite

Question 27

List 11 comorbidities associated with obesity

Answer 27

Depression
Stroke
MI
Sleep apnoea
Hypertension
Diabetes
Bowel cancer
Osteoarthritis
Peripheral vascular disease
Gout