Endocrine Control of Food Intake

Question 1

Which key area of the hypothalamus is involved in the regulation of food intake?

Answer 1

Arcuate nucleus

Question 2

What feature of this area allows it to integrate central and peripheral inputs?

Answer 2

It’s a circumventricular organ (has an incomplete BBB)

Allows access to peripheral hormones

Question 3

What are the 2 neuronal populations in the arcuate nucleus?

Answer 3

Agrp/NPY = stimulatory (increases appetite) 
POMC = inhibitory (decreases appetite)

Question 4

Describe how the melanocortin system works.

Answer 4

Under normal conditions, POMC is broken down to alpha-MSH, which stimulates the MC4R receptor + prevents food intake
When you need to eat, there will be an increase in Agrp activity
Agrp will block the MC4R receptor + stimulate an increase in food intake

Question 5

State 2 CNS mutations that affect this system and can cause obesity.

Answer 5

POMC deficiency: associated with obesity, red hair + pale skin
MC4R mutation: associated with obesity
NO known Agrp or NPY mutations

Question 6

What are 7 features of the leptin deficiency ob/ob mouse?

Answer 6

Obesity 
Diabetes 
Decreased energy expenditure 
Decreased body temperature  
Infertility  
Stunted linear growth  
Decreased immune function

Question 7

What is leptin?

Answer 7

167 AA hormone
Produced by adipocytes + signals to the brain, telling it how much fat there is in storage
High when high body fat

Question 8

What effect does centrally administered leptin have on leptin deficient individuals?

Answer 8

Decreases food intake

Increases thermogenesis

Question 9

What effect does leptin have on the melanocortin system?

Answer 9

Inhibits Agrp/NPY neurones (which increase appetite)
Stimulates POMC (which inhibits appetite)
Result = decrease in energy expenditure

Question 10

What issue do obese people without leptin deficiency have, which means that leptin treatment is not effective as an anti-obesity drug?

Answer 10

Circulating leptin is usually proportional to body fat mass
Most fat humans have high leptin
So a lot of obese people are leptin resistant (doesn’t signal effectively)

Question 11

Why won’t people with leptin deficiency go through puberty?

Answer 11

Leptin has a permissive effect on GnRH release
Without GnRH release, you will not get sufficient LH + FSH release to cause puberty
Also cause of severely underweight getting secondary amenorrhoea

Question 12

Describe the central effects of insulin.

Answer 12

Insulin has a similar effect to leptin as it reduces food intake
There are insulin receptors in the hypothalamus + insulin circulates at levels proportional to body fat
Thus fat people have higher insulin resistance + pancreas must produce more to have an effect

Question 13

What is ghrelin and how is it activated?

Answer 13

Hunger hormone released by the stomach (28 AA’s long)

Activated by Ghrelin-O-acyltransferase (GOAT), which adds a fatty acid to the 3rd AA in the chain

Question 14

What effect does ghrelin have on the melanocortin system?

Answer 14

Stimulates Agrp/NPY neurones
Inhibits POMC neurones
Increases appetite

Question 15

Which cells of the GI tract release PYY and GLP-1?

Answer 15

L-cells

Question 16

What are the effects of PYY3-36? When is it released?

Answer 16

Stimulates POMC neurones
Inhibits NPY neurones
Decreases appetite
Released post-prandially

Question 17

What is GLP-1, what gene encodes it and when is it released?

Answer 17

Glucagon-Like Peptide 1
Encoded by pre-proglucagon gene
Released post-prandially

Question 18

What are the effects of GLP-1?

Answer 18

Important role in the incretin effect: stimulating glucose-stimulated insulin release
Decreases food intake

Question 19

Describe the degradation of GLP-1.

Answer 19

Rapidly broken down by dipeptidyl peptidase-4 (DP-IV)

Half-life: ~1 minute

Question 20

State a long-acting GLP-1 receptor agonist that is used for diabetes and obesity.

Answer 20

Saxenda

Question 21

What is the problem with PYY 3-36 as a drug target?

Answer 21

High levels of PYY can cause nausea

Only a relatively small sweetspot, in terms of concentration, that will have beneficial effects

Question 22

State 8 comorbidities associated with obesity.

Answer 22

Stroke
Depression
Sleep apnoea
MI
Cancer
Diabetes
Hypertension
Osteoarthritis

Question 23

What is the thrifty gene hypothesis?

Answer 23

It was evolutionarily sensible to put on extra weight because it meant that we could survive the times when food was scarce (thinner people would die in these times)

Question 24

What is the adaptive drift hypothesis?

Answer 24

Used to be a normal distribution in terms of body weight
Predators would kill fat people
We improved at evading predators so increased body weight because a neutral change

Question 25

What are 3 profound effects of Leptin deficiency, explaining its name the “hormone of absence”?

Answer 25

Hyperphagia
Lowered energy expenditure
Infertility

Question 26

Why is leptin considered an anti-starvation hormone rather than an anti-obesity hormone?

Answer 26

Presence of leptin tells the brain there is sufficient fat reserves for normal functioning
High leptin has little effect in suppressing appetite

Question 27

What does central administration of insulin result in?

Answer 27

Reduced food intake

Question 28

What are the 3 types of satiety action gut hormones can have?

Answer 28

Post prandial: Release decreases food intake, but takes a while to work
Chronic: Gut diseases may cause chronic elevation to reduce food passing through GI tract
Acute nausea: Toxin ingestion can cause acutely very high levels