Endocrine control of food intake

Question 1

Describe the circuits involved in appetite regulation in the brain?

Answer 1

Balance between food intake and enegry expenditure is balanced by hypothalamus
Input mostly from Ghrelin, PYY, gut hormones, Leptin, and neural input (especially brain stem -vagal (strecth of stomach)

Question 2

Where in the hypothalamus can you find regions responsible for appetite regulation? What are the neurons responsible?

Answer 2

Arcuate nucleus, sitting just above median eminence-incomplete BBB allowing access by peripheral hormones
2 neuronal populations there-stimulating appetite (NPY,Agrp), and inhibiting appetite (POMC neuron)

Both populations extend to hypothalamic and extra-hypothalamic regions

POMC deficiency, or MC4 Receptor mutation leads to morbid obesity (but rare)

Question 3

How does Leptin affect appetite? is there cases of dysfunction?

Answer 3

Leptin-tells your body you are full/not starving
Produced from body fat-and associated with it (when low fat, low lept, High fat, high Lept)
Activates POMC neurons AND inhbits NPT/Argp neurons-reduce hunger
Its more anti-starvation than anti-obesity (absence is more important than presence)
Thought off as long term signal as adipose tissue doesnt change fast

In obesity-raised leptin BUT resistance-present but isnt signalling effectively

Question 4

What are the consequences of Leptin deficiency?

Answer 4

The body believes to be starved all the time-infertile, morbidly obese, immune down, etc
If patients are given Leptin-Not resistant-then lost weight very fast
Also leptin deficient dont go through puberty-Giving replacement Lept helps restore
Can also help restore periods in some hypothalamic ammenorhoae (in thin women with low leptin)

Question 5

Does insulin have a role in food intake/appetite? If yes, which one?

Answer 5

BASAL Insulin circulates at levels proportional to body fat (still spikes after food)
Receptors in the hypothalamus
administration in animals in CNS reduces food intake

Question 6

What is the role of enteroendocrine gut cells in appetite?

Answer 6

Can sense Lipids, carbohydrates, proteins and other nutrients
Depending on WHERE in the gut, and what has been senses-release hormones from basal side
Can be paracrine, modulate neuronal function (like vagus) or classical endocrine function

Question 7

What is ghrelin? what is its role in Appetite?

Answer 7

28aa, but with a wierd carbohydrate chain attatched to it
Released more as you havent eaten for a while
peak just before meals -drives your hunger for food
Stimulates NPY/Agrp, inhbits POMC neurons

Question 8

Where are PYY and GLP-1 released from?

Answer 8

L-cells in the small intestine
usually thin apical, wide basal
Release PYY, GLP-1 and can modulate neurons

Question 9

What is PYY? what is its role in appetite?

Answer 9

PYY-cut into PYY-36
And rises when you eat (proportional to calory intake)-
Inhbits NPY, stimulates POMC -pretty much makes you feel full when you eat-

Question 10

What is the role of GLP-1 in appetite regulation?

Answer 10

Glucagon like peptide-coded by glucagon gene-made from same precursor, just chopped different
Turned off quite fast (cleaves a bit off)
GLP-1 stimulates insulin release (gut telling pancreas (instead of sensing in blood))-but also reduces food intake

used for treatment-either GLP1 agonist
Or inhbit enzyme that breaks down DPP-4
treat T2D -and has now been used to lose weight

Question 11

Can gut hormones be used to treat obesity?

Answer 11

Possibly, but need to be careful because when too high, cause nausea, if too low-no effect
need to hit a sweet spot, and keep it there (not breakdown too fast)