Neurohormonal control of appetite Flashcards
what does the ARC contain
1st order neurons
POMC
CART
AGRP
NPY
role of POMC and CART
inhibits food uptake
ghrelin released from stomach acts on agrp and NPY
POMC (pro-opiomelanocortin)
not a peptide hormone, cannot be secreted
how does POMC act to reduce food intake
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
what does POMC ablation cause
obesity
red hair
hyperphagia
Agouti related peptide (AGRP)
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
where does chronic AGRP project to
PVN
AGRP effect on UCP-1
UCP-1 marks energy expenditure (brown adipose tissue)
AGRP reduces UCP-1
Neuropeptide Y (NPY)
appetite stimulant
increased food intake decreases energy expenditure
influx of NPY causes obesity
6 receptors (Y1-6) Y1,2,5 found in hypothalamus
double KO of AGRP and NPY
no lean phenotype due to developmental compensation
NPY/AGRP contain unidentified appetite regulator
optogenetics
Aponte et al., 2011
light directed at ARC
activates AGRP neurons
induces feeding
cocaine and amphetamine regulated transcript (CART)
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
what is the human CART deficiency
obesity and low basal metabolic rate
counter signals
AGRP/NPY = hunger signal (high leptin inhibits)
POMC/a-MSH = satiety signal (high leptin activates)
MC4R mutants
morbid obesity
>4% children morbidly obese
phenotype: hyperphagia, tall stature, hyperinsulinemia, increased bone mineral density