Extended Data Fig. 2: TGR5 activation in neurons reduces food intake.
From: Central anorexigenic actions of bile acids are mediated by TGR5
a, Quantification of AgRP neurons in the arcuate nucleus of over-night fasted TGR5 wild-type (Gpbar1+/+, 4 animals) and TGR5 knockout (Gpbar1-/-, 3 animals) mice. b, Body weight curve of 8-week-old Gpbar1+/+ and Gpbar1-/- mice over an 8-week period. n = 8 animals. c, Body composition (lean and fat mass expressed as a percentage over the body weight (BW)) of Gpbar1+/+ and Gpbar1-/- mice. n = 10 animals. d, Validation of the TGR5:GFP knock-in mouse model (n = 4 animals) in which the mouse Gpbar1 gene was substituted with a construct containing the human GPBAR1, the F2a sequence and the Gfp. Brains from wild-type mice (n = 3 animals) were used as controls. e, Gpbar1 mRNA levels in arcuate nucleus (ARC)-enriched hypothalamic punches of control mice (Gpbar1fl/fl) and neuron-specific TGR5 knockout (SynCre;Gpbar1fl/fl) mice. n = 8 animals. f, Body weight curve of 8-week-old of control mice (Gpbar1fl/fl, 10 animals) and neuron-specific TGR5 knockout (SynCre;Gpbar1fl/fl, 9 animals) mice over an 8-week period. g, Body composition (lean and fat mass expressed as percentage over body weight (BW)) of Gpbar1fl/fl (n = 10 animals) and SynCre;Gpbar1fl/fl (n = 6 animals) mice. h, 12-hour food intake of Gpbar1fl/fl (n = 7 animals) and SynCre;Gpbar1fl/fl (n = 8 animals) mice. i, Pomc mRNA levels in ARC-enriched hypothalamic punches of Gpbar1fl/fl and SynCre;Gpbar1fl/fl mice. n = 7 (SynCre;Gpbar1fl/fl fasting) and n = 8 (all other groups) animals. j, 12-hour cumulative food intake of control mice (Gpbar1fl/fl) and neuron-specific TGR5 knockout (SynCre;Gpbar1fl/fl) mice after oral administration of INT-777 (100 mg/Kg) or vehicle. n = 5 (Gpbar1fl/fl), n = 8 (SynCre;Gpbar1fl/fl INT-777) and n = 9 (SynCre;Gpbar1fl/fl vehicle) animals. k, Total food intake of Gpbar1fl/fl and SynCre;Gpbar1fl/fl during night and day. n = 6 (Gpbar1fl/fl INT-777 night), n = 7 (Gpbar1fl/fl other groups), n = 8 (SynCre;Gpbar1fl/fl other groups) and n = 9 (SynCre;Gpbar1fl/fl vehicle day) animals. l, 12-hour cumulative food intake of control mice (Gpbar1+/+) and germline TGR5 knock-out (Gpbar1-/-) mice after oral administration of the TGR5 specific BA agonist INT-777 (100 mg/Kg) or vehicle. n = 6 (Gpbar1+/+ vehicle), n = 7 (Gpbar1-/- vehicle) and n = 8 (all other groups) animals. m, Total food intake of Gpbar1+/+ and Gpbar1-/- mice during night and day. n = 7 (Gpbar1-/- vehicle night) and n = 8 (all other groups) animals. Results represent mean ± SEM. n represents biologically independent replicates. Two-tailed Student t-test (d, e, h and i), one-way ANOVA (k and m) or two-way ANOVA (j and l) followed by Bonferroni post-hoc corrections vs. Wild-type (d), Gpbar1fl/fl (e, h and i), Gpbar1fl/fl Vehicle (j and k) or Gpbar1+/+ Vehicle (l and m) were used for statistical analysis. P values (exact value, * P ≤ 0.05 or **** P ≤ 0.0001) are indicated in the figure.
