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. Author manuscript; available in PMC: 2021 Nov 24.
Published in final edited form as: Nat Metab. 2021 May 24;3(5):595–603. doi: 10.1038/s42255-021-00398-4

Figure 1. BAs reach the hypothalamus during physiological feeding and suppress food intake through TGR5.

Figure 1

(a) Conjugated and unconjugated BA species measured in the hypothalamus after 30- and 60-min refeeding in wild-type mice. Bars represent the mean from 8 replicates. n=8 animals. (b) 24-hour food intake after oral administration of BA mix (n=5 animals) or vehicle (n=4 animals). (c) Representative images showing Gpbar1 mRNA (in white) using RNAscope technique in the hypothalamus of TGR5 wild-type (Gpbar1+/+) and germline TGR5 knock-out (Gpbar1−/−) mice. ARC = arcuate nucleus, 3V = third ventricle. Scale bar = 50μm and digital zoom. n=4 animals. (d) INT-777 measurement in the hypothalamus after 30 and 60 min of oral administration of the TGR5 specific BA agonist INT-777 at 3 different doses or vehicle in 8-week-old wild-type mice. n=8 (INT-777 10 and 100 mg/Kg 30 min) and n=7 (all the other groups) animals. (e) One-hour cumulative food intake of wild-type mice after oral administration of the TGR5 specific BA agonist INT-777 at three different doses or vehicle. n=6 (INT-777 100 mg/Kg) and n=8 (all other treatments) animals. (f) mRNA levels of orexigenic genes Agrp and Npy 1 hour after oral (gavage) and intracerebroventricular (icv) administration of INT-777 or vehicle in arcuate nucleus (ARC)-enriched hypothalamic punches of wild-type mice. n=6 animals. (g) Pomc mRNA levels in arcuate nucleus (ARC)-enriched hypothalamic punches of mice described in f. n=6 animals. Results represent mean (a) or mean ± SEM (b, d-g). n represents biologically independent replicates. Two-tailed Student’s t-test (b and f), one-way (d) or two-way ANOVA followed by Bonferroni post-hoc correction (e) vs. vehicle group were used for statistical analysis. P values (exact value, * P ≤ 0.05 or **** P ≤ 0.0001) are indicated in the figure.