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Hypothalamus - Coggle Diagram
Hypothalamus
signals of obesity
alpha melanocortins/aMSH
- melanocyte stimulating hormone
- levels high in hypothalamus
- anorexigenic
neuropeptide y/NPY
- on ARC
- potently orexigenic
agouti related protein/AgRP
- co-expressed with NPY on ARC
- AgRP and agouti are antagonists to aMSH
- orexigenic
-
drugs
past
- noradrenergics
suppress appetite to inhibit noradrenalin uptake
cardiovascular side effects
- serotonergics
suppress appetite through serotonin receptors
induced heart disease
- sibutramine
inhibits noradrenaline, serotonin, dopamine reuptake
cardiovascular and stroke side effects
present
- orlistat
reduces efficiency of fat absorption
sides effects of cramps and diarrhoea and need fat soluble vitamin supplements
- rimonabant
antagonist to cannabinoid receptors
side effects of severe anxiety and depression
new
- lorcaserin
lesser efficacy than past
rejected
- qsymia
better efficacy
rejected
- contrave
effective in patients but cardiovascular concerns
approved
- liraglutide
GLP-1 (satiety) agonist
approved
balance of feeding
orexigenic
ghrelin
appetite stimulant
- lowers food storage and energy use until feeding
anorexigenic
leptin, insulin
appetite suppressant
leptin
- cytokine from adipocyte and relative to fat mass
- high Ob-Rb (receptor) on ARC (hypothalamus neurons)
also involved in
- maintenance of immune and reproductive system
- making blood vessels, tumour and bones
insulin
- relative to fat mass
- high receptors on ARC
leptin resistance
limited application due to leptin resistance in obese people, may be due to:
- defective leptin to brain transport
- altered signal transducation
3 signal cascades:
- JAK2-STAT (transcription reg)
- IRS-PI3K (transcription reg, electric neuronal activity)
- ERK and AMPK
- inhibition of PI3K prevented leptin and insulin pathway
- leptin and insulin resistance was via the PI3K pathway
- SOCS inhibit cytokine signalling incl JAK-STAT
- SOCS3 (reg by STAT) binds to Ob-Rb to prevent leptin signalling
control autonomic and endocrine system for fighting, feeding, fleeing and mating
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