Figure 6. Reduced Vagal Sensitivity to CCK in Obesity Is Associated with Impaired CCK Signaling and CART Expression in NG.
(A) Representative images of CART in DVC from rats fed chow or HFHS diet for 8 weeks. Scale bar, 100 μm.
(B) Quantification of NTS CART is lower in the NTS of HFHS-fed compared with chow-fed rats (n = 4–6; unpaired two-tailed t-test, p = 0.0166).
C) CCK (IP, 2ug/kg) reduces 1 h food intake in chow, but not HFHS, fed rats (n = 5; Two-Way ANOVA, interaction F(1,8) = 5.834, p = 0.04; Sidak’s multiple comparison **p < 0.0085).
(D) EIA quantification of CART protein concentration from pooled left and right NG increases more in response to CCK (IP, 2ug/kg) in chow than HFHS fed rats (n = 5; unpaired two-tailed t-test, p = 0.0048).
(E) c-Fos in the NTS increases more in response to CCK (IP, 2ug/kg) in chow fed compared to HFHS fed rats (n=5; unpaired two-tailed t-test, p = 0.04).
(F) CCKa receptor mRNA expression is lower in the NG of HFHS-fed, compared to chow-fed, rats (n = 11–12; unpaired two-tailed t-test, p = 0.0008).
(G) Representative stitched images of right NG from rats obese rats fed a high fat diet for 8 weeks and switched to chow for 5 months. Dietary intervention failed to rescue low CART expression in NG in DIO rats in both fasted and refed conditions. Scale bar, 100 μm.
(H) Percent CART+ NG neurons remains blunted with re-feeding. (n = 3; unpaired two-tailed t-test p = 0.703)