Endocrine Control of Food Intake

Question 1

Explain the body weight homeostasis

Answer 1

o Ghrelin, PYY & other gut hormones
o Neural input from periphery & other brain regions
o Leptin

ALL INPUT into the HYPOTHALAMUS

Which either
o Food intake
o Energy expenditure

Question 2

Which part of the brain control body weight homeostasis?

Answer 2

Hypothalamus - Arcuate Nucleus

Question 3

Location of the arcuate nucleus?

Answer 3

ONENOTE!!!

Question 4

How does the arcuate nucleus control body weight homeostasis?

Answer 4

Incomplete BBB allows access to peripheral hormones
o integrates peripheral & central feeding signals

2 neuronal populations:
o STIMULATORY –> NPY/Agrp neuron
o INHIBITORY –> POMC neuron

Question 5

Where do the sets of neurons in the arcuate nucleus extend to?

Answer 5

Extend to
o OTHER hypothalamic
o extra-hypothalamic regions

Question 6

Explain the arcuate nucleus flow diagram

Answer 6

LUDLEYS!!

Agrp & POMC axons extend from arcuate nucleus –> paraventricular nucleus

o Agrp INHIBITS MC4R = INCREASE appetite
o POMC cleaved to form alpha-MSH which STIMULATES MC4R = DECREASE appetite

Question 7

Mutations affecting appetite?

Answer 7

NO NPY/Agrp mutations discovered

o POMC deficiency (thus lack of ACTH)
o MC4R mutations
CAN both lead to morbid obesity

Question 8

Ob/Ob Mouse?

Answer 8

Mouse w. a RECESSIVE mutation

o Obese
o Diabetic
o Infertile
o Stunted growth
o DECREASED body oC, energy expenditutre, immune function

Similar abnormalitites to starved animals (-diabetes)

Question 9

What was found in the Ob/Ob mouse that could have led to it being obese?

Answer 9

LEPTIN was missing! (167aa)

the way fat tissue tells the brain that you are NOT starving to death

Question 10

Leptin relationship and how does it work?

Answer 10

Leptin is:
o LOW when body fat is LOW
o HIGH when body fat is HIGH

Central/peripheral administation:
o DECREASES food intake
o INCREASES thermogenesis

It also:
o ACTIVATES POMC
o INHIBITS NPY/Agrp

Question 11

Link between Leptin and obesity?

Answer 11

[Leptin] circulates in plasma proportional to fat mass!

Most obese people have HIGH LEPTIN
SO
Obesity must be due to LEPTIN RESISTANCE!!

SO leptin is INEFFECTIVE as a weight control drug

Question 12

Effects of leptin absence?

Answer 12

Hyperphagia, lowered energy expenditure, sterility (similar to starvation effects)

Can also effect gonadotrophins!

Question 13

What is unique about leptin in terms of starvation & obesity?

Answer 13

It is an anti-STARVATION hormone rather than anti-obesity

i.e. presence of leptin tells brain that one has sufficient fat reseves for normal functioning - high leptin has LITTLE effect

Question 14

Effect of insulin on food intake?

Answer 14

Basal insulin circulated at levels proportional to body fat

o has receptors in the hypothalamus
o central administration REDUCES food intake

Question 15

Ghrelin?

Answer 15

28aa gastric hormone

Has a fatty acid group attached to it
o allows it to cross the BBB
o GOAT (ghrelin O-acyltransferase) enzyne adds fatty acid group to activate it

Question 16

Ghrelin and its effect on food intake?

Answer 16

Levels FALLS DIRECTLY AFTER a meal & then rises
o STIMULATES NPY/Agrp
o INHIBITS POMC
o INCREASES appetite

Question 17

L-cells and its link to food intake?

Answer 17

In the large intestine - secretes PYY and GLP-1

Question 18

Peptide YY (PYY) and its effect on food intake?

Answer 18

Cleaved at position 2-3
o to form PYY3-36 (active form)

Related DIRECTLY to CALORIE LOAD of meal (i.e. more calories you eat, the more PYY released)
o INHIBIT NPY release
o STIMULATE POMC
o DECREASE APPETITE

Question 19

GLP-1 and its effect on food intake?

Answer 19

Glucagon-like peptide-1

Coded by the preproglucagon gene & released post-prandially
o has a SHORT half-life due to the enzyme DP-IV breaking it down fast

Has an INCRETIN ROLE in glucose-stimulated insulin release
o REDUCES food intake

Question 20

Incretin vs. glucose?

Answer 20

If give glucose in GI vs. IC

GI will show a greater response due to INCRETIN so will show a greater release of insulin (vs. the pancreas)

Question 21

Saxenda?

Answer 21

Long-acting GLP-1 receptor agonist (liraglutide)

o double dose for T2DM
o REDUCES food intake

Question 22

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

Answer 22

1. Post-prandial
   - reduces food intake FOLLOWING a meal
2. Chronic
   - gut disease - chronic elevation suppresses appetite
3. Acute nausea
   - toxin ingestion - acutely very high levels