Obesity and the Endocrine Control of Food Intake Flashcards
What does the arcuate nucleus do?
Key brain area involved in regulation o of food intake
Incomplete brain barrier to allow access to peripheral hormones.
The arcuate nucleus acts to integrate central and peripheral feeding signals.
Two neuronal populations:
- Stimulatory (increase appetite) – NPY/Agrp neurons.
- Inhibitory (decrease appetite) – POMC neurons.
Both sets of neurons extend to other hypothalamic regions and extra-hypothalamic regions.
The arcuate nucleus extends its Agrp, POMC axons into the paraventricular nucleus.
Agrp directly inhibits MC4R (melanocortin 4 recptor) to increase appetite.
POMC is cleaved to form alpha-MSH which then stimulates MC4R which decreases food intake.
What are some mutations in NPY/Argp and POMC?
No NPY/Agrp mutations have been discovered
POMC deficiency (thus lack of cortisol) and MC4R mutations can lead to morbid obesity
What does a mutation in the ob gene cause?
obese diabetic infertile stunted linear growth decreased body temperature, energy expenditure and immune function
What was found to be missing in the ob/ob mouse?
leptin
Where is leptin released from?
white adipose tissue
receptors in hypothalamus (Ob-R)
Ob gened codes for hormone leptin
When is leptin found?
Leptin is low when body fat is low and high when body fat is high
Why is leptin inneffective as a weight control drug?
In leptin-deficient people, leptin administration decreased food intake and increased
In most fat humans, they have HIGH leptin, thus obesity could be due to leptin resistance.
Thus, leptin is an ineffective weight control drug
What are the effects of absence of leptin?
Hyperphagia, lowered energy expenditure and sterility – like effects of starvation.
Leptin is an anti-starvation hormone and so presence of leptin tells the brain that one has sufficient fat reserves for normal functioning (but high leptin has little effect).
Where are insulin receptors?
What odes central administration of insulin do?
hypothalamus
reduces food intake
*insulin circulates at levels proportional to body fat
What is ghrelin?
Release of gut hormones is regulated by gut content.
Ghrelin is a 28aa gastric hormone that has a fatty acid group attached that allows it to cross the BBB.
GOAT – Ghrelin O-acyltransferase – this is the enzyme that adds the fatty acid group to ghrelin to activate it.
Ghrelin levels fall directly after a meal and the rise again.
Stimulates NPY/Agrp, inhibits POMC ->Increases appetite.
What is a satiety hormone?
makes you fel full e.g PPY 3-36
What is PYY?
secreted by L cells
PYY is cleaved at position 2-3 to form PYY3-36 – the active form.
PYY levels are related directly to calorie load of the meal.
Inhibit NPY release, stimulate POMC neurons.
Decrease appetite.
What does glucagon like peptide -1 do?
secreted from L cells
Coded for by the preproglucagon gene and released post-prandial.
Has an incretin role in stimulating glucose-stimulated insulin
What’s and example of a long acting GLP-1 receptor agonist?
saxenda
*double dose for T2DM
**reduces food intake
Why is PYY a difficult target for drug manipulation?
narrow therapeutic index
above a certain point -> nausea
