(A) Liraglutide treatment for 28 days in DIO rats significantly increased
mean Cart mRNA levels in the ARC (*P < 0.001
liraglutide vs. vehicle and vs. weight matched), whereas Pomc
expression was unaffected. (B) Npy and
Agrp mRNA levels were significantly increased in weight-matched rats
— but not following treatment with liraglutide (#P
< 0.05 weight matched vs. vehicle and vs. liraglutide). Data are mean ± SEM, and
statistical analyses were performed using 1-way ANOVA, with Fishers post-hoc test.
(C) Voltage-clamp recording of ARC-NPY neurons showed an increased
outward current in the presence of GLP-1(7-36)amide (blue line) and an inward current
with NMDA (red line). (D) Simultaneous GABA receptor inhibition by
bicuculline (black line) showed a lack of change in the current with the addition of
GLP-1(7-36)amide; however, NMDA retained the ability to cause an inward current.
(E) The action of GLP-1(7-36) amide was not directly through GLP-1Rs on
NPY/AgRP neurons, as no colocalization was observed between GLP-1R– (red, yellow
arrows) and NPY/AgRP-positive (green, white arrows) neurons. Scale bars: 100 μm.
(F) The effects of GLP-1(7-36)amide in the presence of bicuculline or
NMDA on ARC-NPY neurons are summarized (mean ± SEM).