🍔Gastro🍔 - Appetite & Thirst

Question 1

What are the common stimuli of thirst?

Answer 1

Body fluid osmolality increases
Blood volume reduced
Blood pressure reduced

Question 2

What is the most potent stimulus for thirst?

Answer 2

Blood fluid osmolality strongest by far

Question 3

What hormone regulates osmolality?

Answer 3

Antidiuretic hormone (ADH)/Vasopressin

Question 4

What is the mechanism of action of ADH?

Answer 4

Acts on the kidneys to regulate the volume & osmolality of urine
Collecting duct - Aquaporin 2 channel
When plasma ADH is low a large volume of urine is excreted (water diuresis)
When plasma ADH is high a small volume of urine is excreted (anti diuresis)

Question 5

Where is ADH stored?

Answer 5

Posterior pituitary gland

Question 6

Which receptors are responsible for the regulation of body fluid osmolality?

Answer 6

Osmoreceptors

Question 7

Outline osmoreceptors

Answer 7

Sensory receptors
Osmoregulation
Found in the hypothalamus

Question 8

Which regions of the hypothalamus are osmoreceptors found?

Answer 8

Organum vasculosum of the lamina terminalis (OVLT)
Subfornical Organ (SFO)

Question 9

How do osmoreceptors detect osmolality and affect ADH release?

Answer 9

Cells shrink when plasma more concentrated (water leaves via osmosis)
Proportion of cation channels increases – membrane depolarizes
Send signals to the ADH producing cells to increase ADH production
Leads to fluid retention and increased thirst
Opposite happens when plasma is less concentrated

Question 10

Explain how the sensation of thirst works

Answer 10

Thirst is decreased by drinking even before sufficient water has been absorbed by the GI tract to correct plasma osmolality
Receptors in mouth, pharynx, oesophagus are involved
Relief of thirst sensation via these receptors is short lived
Thirst is only completely satisfied once plasma osmolality has decreased or blood volume or arterial pressure corrected

Question 11

Explain how the body reacts to decreased blood pressure, in the context of fluid homeostasis

Answer 11

BP decreases sensed by juxtaglomerular cells - secrete renin
Activates renin-angiotensin system
Angiotensin II Stimulats thirst, vasoconstriction by increasing sympathetic activity, ADH and aldosterone secretion
Aldosterone causes H2O retention via
Na+CL- absorption and K+ excretion

Question 12

What is the overarching mechanism for body weight homeostasis?

Answer 12

Question 13

Using the “Biggest Loser” tv show as a study, what phenomenon was exhibited by the contestants that meant most returned to somewhere near their “pre-diet” weight?

Answer 13

Metabolic adaptation to dieting
Decreased caloric intake lead to a long-term reduction in resting metabolic rate

Question 14

Which area of the brain is responsible for homeostasis of food intake and energy expenditure?

Answer 14

Hypothalamus
Lateral hypothalamus (feeding centre) - stimulates food intake
Ventromedial hypothalamus (satiety centre) - suppresses appetite
Paraventricular nucleus - integrates orexigenic (appetite-stimulating) and anorectic (appetite-suppressing) signals
Arcuate nucleus - key area for processing feeding signals

Question 15

Which inputs influence the hypothalamus in the context of balancing food intake and energy expenditure?

Answer 15

Gut hormones - ghrelin, PYY, GLP-1, and others
Neural input - from peripheral systems and other brain regions
Leptin - hormone involved in signalling satiety and energy balance

Question 16

Outline the arcuate nucleus in more detail

Answer 16

The arcuate nucleus is crucial in food intake regulation
Unique features:
-An incomplete blood-brain barrier, allowing interaction with peripheral hormones
-Integrates signals from the body (periphery) and brain (central)
Two types of neurons in the arcuate nucleus:
-NPY/AGRP neurons - stimulate appetite
-POMC neurons - suppress appetite

Question 17

Which neuronal population in the arcuate nucleus will leptin stimulate?

Answer 17

POMC neurons to suppress appetite

Question 18

Outline the effects of AGRP and POMC neurons on the melanocortin system

Answer 18

Question 19

What other brain regions can influence food intake and energy expenditure?

Answer 19

Higher centres - Amygdala - emotion, memory
Other parts of the hypothalamus, e.g. lateral hypothalamus
Vagus to brain stem to hypothalamus

Question 20

What hormone other than leptin is produced by fat?

Answer 20

Adipostat

Question 21

What is the mechanism of adipostat?

Answer 21

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

Question 22

What is leptin?

Answer 22

Circulates in plasma
Acts on the hypothalamus regulating appetite (intake) and thermogenesis (expenditure)

Question 23

Where is leptin secreted and what is its actions?

Answer 23

Secreted from white adipose tissue & gastric mucosa
Reflects energy reserves:
Low when low body fat
High when high body fat
Also increases acutely post-prandially (gastric source)
Decreases food intake and increases thermogenesis

Question 24

What problems with leptin can arise?

Answer 24

Decreased leptin expression/secretion in adipose tissue
Leptin receptor absence
Reduced sensitivity of leptin receptor

Question 25

How does leptin resistance arise?

Answer 25

Leptin circulates in plasma in concentrations proportional to fat mass
Overweight humans have chronically high levels of leptin - leads to resistance (just like insulin)
Obesity due to leptin resistance –
hormone is present but doesn’t signal effectively

Question 26

Why is leptin ineffective as a weight control drug?

Answer 26

Increasing leptin levels will cause leptin receptors to become less sensitive to it

Question 27

What is responsible for short term regulation of appetite (i.e. following a meal)?

Answer 27

Gut hormones

Question 28

What are the gastrointestinal (gut) hormones?

Answer 28

Ghrelin - stimulates appetite
Peptide YY (PYY) and GLP-1
Secreted byenteroendocrine cellsin thestomach, pancreas & small bowel
Control various functions of digestive organs

Question 29

Outline ghrelin

Answer 29

Blood levels of ghrelin are highest before meals - help prepare for food intake by increasing gastric motility and acid secretion
Increases appetite
Involved in regulation of reward, taste sensation, memory & circadian rhythm

Question 30

How does ghrelin modulate neurons?

Answer 30

Directly modulates neurons in the arcuate nucleus:
-Stimulates NPY/AGRP neurons.
-Inhibits POMC neurons.

Question 31

Outline PYY

Answer 31

Short peptide released in the terminal ileum (TI) and colon in response to feeding (36 Amino acids)
Reduces appetite – can be digested or injected IV
Food arriving to the TI and colon results in PYY release

Question 32

What effect does PYY have on neurons?

Answer 32

Stimulates POMC neurons
Inhibits NPY release

Question 33

Outline GLP-1

Answer 33

Short peptide released in the gut in response to feeding (30 Amino acids)
Reduces appetite
Incretin – increases insulin release in response to ingested glucose

Question 34

What are the comorbidities associated with obesity?

Answer 34

Question 35

How does genetics link to obesity?

Answer 35

Monogenic obesity is very rare (<0.1%)
Genetic factors can explain over 40% of the variance in obesity
Around 250 genes are associated with obesity
‘Thrifty genes’ designed to protect us from starvation by allowing us to store energy when food is abundant
Environmental factors can also affect expression of genes via ‘epigenetics’