Gut-Brain Axis Flashcards
role of ghrelin
increases food intake
where is the ARC situated
at the leaky BBB
types of neurons the ARC contains
orexigenic neurons: AGRP NPY
anorectic neurons: POMC/CART
what is ghrelin
28 aa hormone
secreted from the duodenum
requires an octanol group
agonist at the GHS-Rla receptor
meal initiator - plasma levels spike prior to meal
where is the site of action for ghrelin
increased ca2+ release
ghrelin response greatest in NPY+ neurons
other role of ghrelin
impacts memory ?
IV infusion of ghrelin in humans
increases energy intake (kJ)
Wren et al., 2001
GHS-RIa antagonists
stop ob/ob mice eating and reduce body weight
orally available
risk of off target effects on the GH axis
L cell secretion
PYY
Neurotensin
GIP
GLP-1/2
OXM
cause feeling of fullness via vagus nerve
PYY
36 aa
produced in L cells (small and large intestine)
aa 1 and 2 (pro and tyr) cleaved in response to DPP4 forms PYY3-36 (truncated) vs PYY1-36
functions mainly in ileum
Y2R agonist in ARC
post-prandial secretion of PYY
satiety signal
obese - very less PYY release
lean
bypass - most PYY release (Le roux et al., 2005)
what occurs after bariatric surgery
GLP-1 enhanced (more effect than banding)
PYY receptor selectivity
1-36 Y1&Y5 (decreases food uptake)
3-36 Y2 (inhibits food uptake responds to fasting)
what occurs if vagus nerve is severed
reduction in PYY3-36 effect
PYY therapeutic issues
high levels cause narrow therapeutic window
short half life
IV administration impractical requires oral
prevents breakdown due to long lasting analogues which inhibit cumulative food intake
