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. 2023 Apr 12;12:e82649. doi: 10.7554/eLife.82649

Figure 1. Suppressing GABAA signaling reverses feeding and metabolic dysfunction induced by leptin deficiency in AgRP neurons.

(A,B) Expression of tdTomato in the arcuate nucleus with injection of NB124 into the 3rd ventricle for both Agrp+/+::Leprlox/lox::NeoR::Rosa26fs-tdTomato mice (control, (A)) and AgrpnsCre/+::Leprlox/lox::NeoR::Rosa26fs-tdTomato mice (Agrp-Lepr KO, (B)). Scale bar in B for A and B, 200 μm. (C–E) Colocalization of tdTomato (C) and anti-AgRP (D) in ARC. Scale bar in E for C–E, 100 μm. (F) Real-time qPCR analysis of Lepr transcript levels within the AgRP neurons of the control and Agrp-Lepr KO mice. (n=8 per group; *p<0.05). (G–I) Daily calorie intake (G) and body weight (H) of the control and Agrp::LeprKO mice. The GTT (I) was tested on the day 21 after injection of NB124. (n=8 per group; *p<0.05). (J) The 4-hr food intake by the control and Agrp-Lepr KO mice after chronic infusion of Bic (1 ng) into the 3rd ventricle for 4 weeks. (K) Feeding efficiency is presented as mg of body weight gain/kcal consumed in the mice as described in J. (L) Weight of adipose tissues in the mice as described in J (Visc WAT: visceral white adipose tissue; BAT: brown adipose tissue). (M) Average value for RQ (defined as ratio of VCO2/VO2) tested on Day 28 in the mice as described in J. (N) The GTT was performed in the mice as described in J. (n=8 per group in J–N; *p<0.05 between Control and Agrp-Lepr KO, #p<0.05 between Control and Control +Bic(i.c.v.), ‡p<0.05 between Agrp-Lepr KO and Agrp-Lepr KO +Bic(i.c.v.)). Error bars represent mean ± SEM. unpaired two-tailed t test in F; one-way ANOVA and followed by Tukey comparisons test in J–M; two-way ANOVA and followed by Bonferroni comparisons test in G–I, and N.

Figure 1—source data 1. The original data of body weight, food intake, and GTT for Figure 1.

Figure 1.

Figure 1—figure supplement 1. Representative images of the arcuate nucleus with injection of vehicle into the 3rd ventricle for both Agrp+/+::Leprlox/lox::NeoR::Rosa26fs-tdTomato mouse (A) and AgrpnsCre/+::Leprlox/lox::NeoR::Rosa26fs-tdTomato mouse (B).

Figure 1—figure supplement 1.

Scale bar in A for A and B, 200 μm.

Figure 1—figure supplement 2. Representative images of pSTAT3 immunofluorescent staining in the ARC of fasted control and Agrp-Lepr KO mice with vehicle (A–F) or leptin i.c.v injections (G–L).

Figure 1—figure supplement 2.

The percentage of pSTAT3 +in AgRP neurons are quantified (M). (n=8 per group).

Figure 1—figure supplement 3. Representative images of pSTAT3 immunofluorescent staining in the DMH and VMH of fasted control and Agrp-Lepr KO mice with vehicle (A–B, E–F) or leptin i.c.v injections (C–D, G–H).

Figure 1—figure supplement 3.

The number of pSTAT3 +neurons from unilateral side are quantified (I). (n=8 per group).