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

Figure 4. The leptin-responsive AgRP-DMH circuit regulates feeding, body weight, and glucose tolerance.

(A,B) 1-hr food intake (A) and GTT (B) after photostimulation of the AgRP→DMH circuit. (n=8 per group; *p<0.05). (C,D) 1-hr refeeding test (C) and GTT (D) after photostimulation of the MC4RDMH neurons. (n=8 per group; *p<0.05). (E–G) Daily food intake (E), body weight (F) and GTT (G) in control mice, Agrp-Lepr KO mice with Bic or vehicle injected into the DMH. The saline or Bic (4 ng; 0.25 μl/hr) was chronically infused into the DMH via the osmotic minipump for 14 days. (n=8 per group; *p<0.05 between Control and Agrp-Lepr KO, #p<0.05 between Agrp-Lepr KO and Agrp-Lepr KO +Bic(DMH), ‡p<0.05 between Control and Control +Bic(DMH)). (H) 4-hr food intake in the mice described in E-G on day 14. (I) Feed efficiency in the mice described in E–G. (J) Weight of adipose tissues in the mice described in E–G on day 14. (K) Average value for RQ (VCO2/VO2) in the mice described in E–G on day 14. (n=8 per group in H–K; *p<0.05 between Control and Agrp-Lepr KO, #p<0.05 between Agrp-Lepr KO and Agrp-Lepr KO +Bic(DMH)). (L–O) Firing rate of representative MC4RDMH neurons and non-MC4RDMH neurons when mice under baseline (satiation) (L, N), foraging (prior to meal initiation) (M), and glucose i.p. injection (well-fed state) (O). The statistical analysis of the firing rate under baseline, foraging (P), and glucose treatment (Q) were calculated. (n=10 neurons from 3 mice in each group; *p<0.05). Error bars represent mean ± SEM. unpaired two-tailed t test in A, C, P and Q; one-way ANOVA and followed by Tukey comparisons test in H–K; two-way ANOVA and followed by Bonferroni comparisons test in B and D–G.

Figure 4—source data 1. The original data of body weight, food intake, GTT, and firing rate of MC4R neurons in the DMH for Figure 4.

Figure 4.

Figure 4—figure supplement 1. Immunostaining of Fos and WGA-ZsGreen in the DMH of AgrpCre::Roas26fs-ChR2 mice with (E–G) or without (A–C) optogenetic activation of AgRP fiber in the DMH.

Figure 4—figure supplement 1.

The Fos expression in the ARC was examined with (H) or without (D) optogenetic activation of AgRP fiber in the DMH. Scale bars in A for A–H, 100 µm. (I) The percentage of overlay between Fos and Mc4r in the DMH of the mice as described in A–H. (J) The number of Fos +neurons from bilateral sides of ARC (n=8 per group; *p<0.05; unpaired two-tailed t test).

Figure 4—figure supplement 2. The Fos expression in the DMH and other brain regions after infusing Bic into DMH.

Figure 4—figure supplement 2.

(A–F) Representative images of Fos inmmunostaining in the DMH (A–B), PLH (C–D), and PBN (E–F) of Agrp-Lepr KO mice with Bic or vehicle injected into the DMH. The saline or Bic was chronically infused into the DMH via the osmotic minipump. Scale bars in A for A–F, 200 µm. (G) Statistic data about the number of Fos +neurons from unilateral side in the mice described in A–F. (n=6 per group; *p<0.05; unpaired two-tailed t test).