endocrine control of food intake

Question 1

describe the structure of the arcuate nucleus. what is its function?

Answer 1

• incomplete brain barrier to allow access to peripheral hormones
• acts to integrate central and peripheral feeding signals

Question 2

what are the 2 neuronal populations in the arcuate nucleus?

Answer 2

• stimulatory (inc. appetitie): NPY/Agrp neurones

- inhibitory (dec. appetitie): POMC neurones

Question 3

where do these neurones project to?

Answer 3

agrp, POMC axons extend into paraventricular nucleus

Question 4

what does agrp do?

Answer 4

directly inhibits MC4R to inc. appetitie

Question 5

what happens to POMC?

Answer 5

cleaved to form alpha-MSH which then stimulates MC4R which dec. food intake

Question 6

what is the result of mutations in these?

Answer 6

• no NPY/Agrp mutations have been discovered

- POMC def (so lack of cortisol) and MC4R mutations can lead to morbid obesity

Question 7

describe the Ob/Ob mouse

Answer 7

• recessive mutation
• characteristics: obese, diabetic, infertile, stunted linear growth, dec. body temp, energy expenditure, immune function
• found leptin was missing from Ob/Ob mouse

Question 8

when is leptin level low?

Answer 8

leptin is low when body fat is low

Question 9

in leptic deficient people, what does leptin admin do?

Answer 9

• dec. food intake

- inc. thermogenesis

Question 10

in terms of leptin, what could obesity be due to?

Answer 10

leptin resistance
most fat humans have high leptin
so leptin is ineffective weight control drug

Question 11

link leptin to POMC and NPY/Agrp

Answer 11

leptin activated POMC and inhibited NPY/Agrp

Question 12

what are the effects of the absence of leptin?

Answer 12

• hyperphagia
• lowered energy expenditure and sterility
• like effects of starvation

Question 13

what does the presence of leptin tell the brain?

Answer 13

• anti-starvation hormone

- presence of leptin tells brain that one has sufficient fat reserves for normal functioning

Question 14

describe the levels of insulin. where are insulin receptors?

Answer 14

• insulin circulates at levels proportional to body fat
• insulin receptors are in hypothalamus
• central admin reduces food intake

Question 15

what is ghrelin?

Answer 15

28aa gastric hormone

has a fatty acid group attached that allows it to cross BBB

Question 16

what is the enzyme that adds the fatty acid group to activate it?

Answer 16

GOAT (ghrelin O-acyltransferase)

Question 17

what does ghrelin do?

Answer 17

• stimulates NPY/Agrp
• inhibits POMC
• inc. appetite
• levels fall directly after a meal and then rise again

Question 18

where are L cells and what do they secrete?

Answer 18

conical shaped cells in large intestine

secrete PYY and GLP-1

Question 19

how does PYY become active?

Answer 19

PYY cleaved at position 2-3 to form PYY3-36 = active form

Question 20

what does PYY do?

Answer 20

• PYY levels related directly to calorie load of meal
• inhibit NPY release
• stimulate POMC neurones
• dec. appetite

Question 21

what is GLP-1 coded by? when is it released?

Answer 21

• coded for by preproglucagon gene

- released post-prandial

Question 22

what is the role of GLP-1?

Answer 22

• incretin role in stimulating glucose-stimulates insulin release to reduce food intake

Question 23

what is saxenda?

Answer 23

• long acting glucagon-like peptide 1 receptor

- reduces food intake

Question 24

why is PYY3-36 a difficult target for drug manipulation?

Answer 24

narrow therapeutic window

people react differently to levels in system

Question 25

what is the thrifty gene hypothesis?

Answer 25

• specific genes are selected for to inc. metabolic efficiency and fat storage
• makes evolutional sense to put on weight

Question 26

what is the drifty gene hypothesis?

Answer 26

normal distribution of body weight

fat people eaten, thin starved