Extended Data Fig. 1: BA mix and INT-777 reach the hypothalamus after oral or icv administration, respectively, and reduce food intake by activating TGR5.
From: Central anorexigenic actions of bile acids are mediated by TGR5
a, Conjugated and unconjugated BA species measured in the hypothalamus 30- and 60-min after oral administration of a BA mix at three different doses or vehicle in wild-type mice (n = 8 animals). Bars represent the mean from 8 replicates. b, One-hour cumulative food intake of wild-type mice after oral administration of a BA mix at three different doses or vehicle. n = 8 (Vehicle and 1 mg/Kg) and n = 10 (10 mg/Kg and 100 mg/Kg) animals. c, Gpbar1 mRNA levels in arcuate nucleus (ARC)-enriched hypothalamic punches of TGR5 wild-type (Gpbar1+/+) and germline TGR5 knockout (Gpbar1-/-) mice. n = 8 animals. d, One-hour (1 h) food intake measured after the first i.c.v injection (d1 – 1 h) of vehicle (n = 8 animals) or INT-777 (n = 9 animals) in wild-type mice. e, Two-hour (2 h) food intake measured after the first i.c.v injection (d1 – 2 h) of vehicle (n = 8 animals) or INT-777 (n = 9 animals) in wild-type mice. f, Food intake measured after a daily (right before the dark phase) i.c.v injection of vehicle (n = 8 animals) or INT-777 (n = 9 animals) in wild-type mice at the indicated time points. g, Body weight change (expressed as a percentage of the initial body weight) of vehicle (n = 8 animals) or INT-777 (n = 9 animals) in wild-type mice at the indicated time points. Results represent mean (a) or mean ± SEM (b-g). n represents biologically independent replicates. Two-tailed Student t-test (c, d and e) or two-way ANOVA followed by Bonferroni post-hoc correction (b) vs Vehicle (b, d-e) or Gpbar1+/+ (c) were used for statistical analysis. P values (exact value, * P ≤ 0.05 or **** P ≤ 0.0001) are indicated in the figure.
