Neurohormonal control of appetite

Question 1

what does the ARC contain

Answer 1

1st order neurons
POMC
CART
AGRP
NPY

Question 2

role of POMC and CART

Answer 2

inhibits food uptake
ghrelin released from stomach acts on agrp and NPY

Question 3

POMC (pro-opiomelanocortin)

Answer 3

not a peptide hormone, cannot be secreted

Question 4

how does POMC act to reduce food intake

Answer 4

increased leptin and adiposity binding to receptors increases POMC
POMC is a precursor of a-MSH
a-MSH binds to melanocortin 4 receptor (MC4R) reduces appetite (2nd order signalling)
a-MSH reduces food intake

Question 5

what does POMC ablation cause

Answer 5

obesity
red hair
hyperphagia

Question 6

Agouti related peptide (AGRP)

Answer 6

homologue for agouti protein which causes yellow hair
AGRP coexpressed with NPY in ARC
AGRP is an endogenous antagonist of MC3R & MC4R - blocks a-MSH binding

Question 7

where does chronic AGRP project to

Answer 7

PVN

Question 8

AGRP effect on UCP-1

Answer 8

UCP-1 marks energy expenditure (brown adipose tissue)
AGRP reduces UCP-1

Question 9

Neuropeptide Y (NPY)

Answer 9

appetite stimulant
increased food intake decreases energy expenditure
influx of NPY causes obesity
6 receptors (Y1-6) Y1,2,5 found in hypothalamus

Question 10

double KO of AGRP and NPY

Answer 10

no lean phenotype due to developmental compensation
NPY/AGRP contain unidentified appetite regulator

Question 11

optogenetics

Aponte et al., 2011

Answer 11

light directed at ARC
activates AGRP neurons
induces feeding

Question 12

cocaine and amphetamine regulated transcript (CART)

Answer 12

coexpressed with POMC in ARC
food deprived (low leptin=reduced ARC)
not present in obese animals (ob/ob db/db)
administering leptin increases CART
CART decreases normal/starvation induced feeding, blocks feeding response from NPY

Question 13

what is the human CART deficiency

Answer 13

obesity and low basal metabolic rate

Question 14

counter signals

Answer 14

AGRP/NPY = hunger signal (high leptin inhibits)
POMC/a-MSH = satiety signal (high leptin activates)

Question 15

MC4R mutants

Answer 15

morbid obesity
>4% children morbidly obese
phenotype: hyperphagia, tall stature, hyperinsulinemia, increased bone mineral density

Question 16

thyrotropin releasing hormone TRH

Answer 16

peptide secreted by PVN, downregulated during fasting
leptin increases production of a-MSH, stimulates TRH release
acts on anterior pituitary , releases TSH, which releases TH from the thyroid gland (increases energy expenditure)
a-MSH increases TSH via leptin
AGRP inhibits and blocks TSH

Question 17

melanin concentrating hormone MCH - orexigenic

Answer 17

overexpressed in ob/ob mutants
fasting increases MCH in obese and normal mice
MCH injected in lateral ventricles increases food consumption
MCH KO leanness and reduced body weight- reduced feeding and increased metabolic rate

Question 18

orexins A and B (hypocretins) - orexigenic neurons

Answer 18

exclusively produced in the lateral hypothalamic area (LHA)
orexin deficiency causes nacrolepsy (irregular sleep wake cycle)
regulated by ghrelin/leptin/glucose

Question 19

3 regions which receive input from AGRP neurons

Answer 19

POMC neurons in ARC
parabrachial nucleus (PBN) in hindbrain
paraventricular hypothalamus (PVH) neurons

Question 20

PVH lesions

Answer 20

cause hyperphagia and obesity
inhibition in PBN promotes feeding, rescues aphagia

Question 21

AGRP and OT (from PVH) circuit

Answer 21

increased food intake
PVH is heterogenous
OT is anorexigenic
OT loss of function is implicated in Prader Willi Syndrome

Question 22

what is required for AGRP induced food intake

Answer 22

NPY and GABA release from AGRP