Action of Leptin Flashcards
What do falling serum leptin levels indicate?
That the body is starving - therefore it drice hunger and suppresses energy expenditure.
Explain how the leptin pathway leads to suppression of appetite.
1) Leptin binds to leptin receptors in the hypothalamus.
2) Causes release of neuronal signals to the region of the brain that suppresses appetite.
3) Once stimulated by leptin - the hypothalamus directs signals via a sympathetic neurone to increase thermogenesis in adipose tissue,
4) The uncoupler protein 1 dissipates heat in thermogenesis - energy of the proton gradient is dissipated without being stored as ATP.
Outline what happens when fat stores are high.
Lots of leptin.
CART.
POMC - AMSH - MC4R - (TRH - TSH - TH - decrease metabolic rate) and - (CRH - ACTH - Cortisol - decrease appetite) - DECREASE WEIGHT.
Also…
Inhibit NPY - inhibit inhibition of POMC.
Inhibit AGRP - inhibit inhibition of AMSH binding to MC4R.
What happens when fat stores are low?
less leptin.
Increase NPY - inhibit POMC
Increase AGRP - inhibit AMSH binding to MC4R.
NPY also - orexin and MCH which increases weight.
What is CART?
Cocaine and amphetamine regulated transcript.
Not much known about its receptor but it is coexpressed with POMC and is thought to have similar actions.
ARC
What is POMC?
Proopiomelanocortin. It is processed to form AMSH.
Its actions are inhibited by NPY binding to Y1P receptors on POMC neurones.
Abormal POMC gene - red hair, hyperphagia and obesity.
ARC
What is AMSH?
Alpha - melanocyte stimulating hormone.
Agonist at MC4R.
ARC
What is MC4R?
Melanocortin 4 receptor Mutations... - monogenic obesity - hyperphagia - tal - hyperinsulinemia - increased bone mineral density
Stimulates TRH, CRH.
PVN
What is TRH
Thyrotropin releasing hormone
From hypothalamus.
–> TSH
PVN
TSH?
Thyroid stimulating hormone
From AP
–> thyroid hormone.
PVN
Thyroid hormone?
Increase metabolic rate - decrease weight!
PVN
CRH?
Corticotropin releasing hormone
Hypothalamus
—> ACTH
PVN
ACTH?
Adrencorticotrophic hormone
From AP
—> cortisol
PVN
Cortisol?
Adrenal glands…decrease appetite, decrease weight.
PVN
NPY?
Neuropeptide - binds to YP1 on POMC neurones to prevent anorexigenic action. Stimultaes orexin and MCH.
ARC
