Endo 14: Obesity ++ endocrine control of food intake Flashcards
Wha the function of arcuate nucleus ?
- involved in the regulation of food intake
–> integrates peripheral and central feeding signals
What is meant by the fact that the arcuate nucleus is a circumventricular organ?
- means it has an incomplete BBB
- -> therefore allowing access to peripheral hormones
What are the 2 types of neuronal populations in the arcuate nucleus?
a) STIMULATORY - inc app
- NPY + AGRP neurons
b) INHIBITORY - dec app
- POMC neurons
in normal conditions, what happens in the melanocortin system?
- POMC = broken down to a-MSH
- -> which is an endogenous agonist of MC4R
–> so ur not hungry all the time
When you need to eat you increase/ decrease Agrp activity
and block the inhibitory/stimulatory signal of a-MSH and stimulate food intake
When you need to eat you increase Agrp activity
and block the inhibitory signal of a-MSH and stimulate food intake
POMC deficiency + MC4-R mutation causes:
POMC deficiency + MC4-R mutation causes: morbid obesity
What is the function of leptin ?
- leptin = released from fat cells
- activates POMC + inhibits NYP/Agrp neurons
- -> tells brain how much fat is in storage
- -> therefore regulating eating
What is a characteristic of leptin deficiency?
- patients with leptin deficiency will think they are starving all the time
central / peripheral administration of leptin causes increase / decrease in food intake
and
increase / decrease in thermogenesis
central / peripheral administration of leptin causes decrease in food intake
and
increase in thermogenesis
Why is leptin ineffective as a weight control drug?
- because most obese people = obese resistant
- -> they have leptin
- -> but doesn’t signal effectively
in what situation may leptin administration be useful?
for those with leptin DEFICIENCY
what might be the consequences of absence of leptin?
- hyperphagia
- lowered energy expenditure
- sterility
What role does insulin have on food intake?
- circulating insulin levels = proportional to body fat
- there are insulin receptors in the hypothalamus
- insulin signals similarly to leptin
so central administration of insulin (directly into brain) –> reduces food intake
What is ghrelin?
- hunger hormone
- released by stomach
- 28 a.acid long
ghrelin is converted to its active form by the enzyme ________________
ghrelin is converted to its active form by the enzyme Ghrelin O- Acyltransferase (GOAT)
note: levels of ghrelin drops after each meal then gradually increases until the next meal
-
How does ghrelin increase appetite?
- directly modulates neurons in the arcuate nucleus
- STIMULATES Agrp/NPY neurons
- INHIBITS POMC neurons
- -> increases appetite
What are PYY + GLP-1 secrete by?
- secreted by L cells in the distal s. intestine + colon
How does PYY hormone work?
- PYY = released post-prandially
- directly modulates neurones in the arcuate nucleus
- it is a fullness hormone
- PYY decreases appetite
- -> inhibits NPY release
- -> stimulates POMC neurons
How does GLP-1 hormone work?
- coded for by preproglucagon gene
- released post prandially (after eating)
- GLP1 = released after eating meal
- has incretin effect
- stimulates insulin secretion from the pancreas
( glucose induced insulin release ) - and reduces food intake
How is GLP-1 degraded ?
- quickly inactivated by DP-4
What is Saxenda?
- it is a long acting GLP-1 receptor agonist
- GLP-1 structure = modified –> so that it is more resistant to degradation
How is the half life of saxenda prolonged?
- it has a fatty acid group attached –> which stops it from being cleared from the circulation
–> which gives it a much longer half life
What are other uses of Saxenda ?
treatment for:
- diabetes
- obesity
