Neurohormonal control of appetite Flashcards

1
Q

what does the ARC contain

A

1st order neurons
POMC
CART
AGRP
NPY

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2
Q

role of POMC and CART

A

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

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3
Q

POMC (pro-opiomelanocortin)

A

not a peptide hormone, cannot be secreted

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4
Q

how does POMC act to reduce food intake

A

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

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5
Q

what does POMC ablation cause

A

obesity
red hair
hyperphagia

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6
Q

Agouti related peptide (AGRP)

A

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

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7
Q

where does chronic AGRP project to

A

PVN

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8
Q

AGRP effect on UCP-1

A

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

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9
Q

Neuropeptide Y (NPY)

A

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

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10
Q

double KO of AGRP and NPY

A

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

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11
Q

optogenetics

Aponte et al., 2011

A

light directed at ARC
activates AGRP neurons
induces feeding

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12
Q

cocaine and amphetamine regulated transcript (CART)

A

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

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13
Q

what is the human CART deficiency

A

obesity and low basal metabolic rate

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14
Q

counter signals

A

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

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15
Q

MC4R mutants

A

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

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16
Q

thyrotropin releasing hormone TRH

A

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

17
Q

melanin concentrating hormone MCH - orexigenic

A

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

18
Q

orexins A and B (hypocretins) - orexigenic neurons

A

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

19
Q

3 regions which receive input from AGRP neurons

A

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

20
Q

PVH lesions

A

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

21
Q

AGRP and OT (from PVH) circuit

A

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

22
Q

what is required for AGRP induced food intake

A

NPY and GABA release from AGRP