Colonic 5-HT is increased in male mice with diabetes. (A) Body weight and (B) fasting blood glucose levels of male and female C57BL/6J mice fed a ND or HFHSD measured for four months (n = 6 to 13 mice). (C) Glucose tolerance tests and (D) insulin tolerance tests of male and female C57BL/6J mice fed a ND or HFHSD (n = 7 to 10 mice). (E) Serum 5-HT (n = 8 to 11 mice) and (F) colonic tissue 5-HT levels (n = 3 to 6 mice) of male and female C57BL/6J mice fed a ND or HFHSD. (G) Representative colonic tissue histology from tamoxifen injected Tph1-tdTom mice (scale bars = 300 μm). (H) Colonic Tph1+ cell density of male and female Tph1-tdTom mice fed a ND or HFHSD (n = 3 to 5 mice). (A, B, C, D) 3-way ANOVA, Tukey’s multiple comparisons test, and (E, F, H) 2-way ANOVA, Sidak’s multiple comparisons test were used. *P < 0.05, **P < 0.01, ***P < 0.001 vs ND male mice; #P < 0.05, ###P <0.001 vs ND female mice.