Figure 2. TGR5 is expressed in neurons and its deletion increases food intake.
(a) 24-hour cumulative food intake of 8-week-old TGR5 wild-type (Gpbar1+/+, n=6 animals) and germline TGR5 knock-out (Gpbar1−/−, n=7 animals) mice. (b) 12-hours food intake of Gpbar1+/+ (n=8 animals) and Gpbar1−/− (n=7 animals) mice. (c) mRNA levels of orexigenic genes Agrp and Npy after overnight fasting and fed conditions in arcuate nucleus (ARC)-enriched hypothalamic punches of Gpbar1 +/+ and Gpbar1 −/− mice. n=8 animals. (d) Pomc mRNA levels in arcuate nucleus (ARC)-enriched hypothalamic punches of mice described in c. n=8 animals. (e) Generation of transgenic mice expressing TGR5 and Green Fluorescent Protein (GFP) under the control of the mouse Gpbar1 promoter (TGR5:GFP), and hypothalamic immunodetection of the neuronal marker NeuN in red, TGR5 (GFP) in green and nuclei staining (DAPI) in blue, in TGR5 wild-type (Wild-type) and TGR5:GFP mice. Scale bar = 20 μm. n=4 animals. (f) 24-hour cumulative food intake of Gpbar1fl/fl and SynCre;Gpbar1fl/fl mice. n=8 animals. (g) mRNA levels of orexigenic genes Agrp and Npy after overnight fasting and normal fed conditions in arcuate nucleus (ARC)-enriched hypothalamic punches of Gpbar1fl/fl and SynCre;Gpbar1fl/fl mice. n=8 animals. Results represent mean ± SEM. n represents biologically independent replicates. Two-tailed Student’s t-test (b, c, d and g), or two-way ANOVA followed by Bonferroni post-hoc correction (a and f) vs. Gpbar1+/+ (a-c), fasting (d) or Gpbar1fl/fl (f and g) groups were used for statistical analysis. P values (exact value, * P ≤ 0.05 or **** P ≤ 0.0001) are indicated in the figure.
