Vasoactive intestinal polypeptide (VIP) density indices were reduced in 20-week HF diet mice, compared to 20-week SC. VIP IR in muscularis externa (a–b) and LMMP (c–d) were used to assess density indices of IR in nerve fibers and ganglia of muscularis externa (“muscularis”), and myenteric ganglia of LMMP in 20-week SC diet (a, c) and HF diet (b, d) mice. Compared to 20-week SC diet mice, VIP density indices of 20-week HF diet mice were reduced in both the muscularis externa (e; P = 0.012, n = 8, unpaired t-test) and in the myenteric ganglia (f; P = 0.012, n = 8, unpaired t-test).