Extended Data Fig. 1: Pharmacological NMDA receptor antagonism dose-dependently lowers body weight but induces hyperthermia.
From: GLP-1-directed NMDA receptor antagonism for obesity treatment
a-f, Treatment of C57BL/6 J DIO mice with once-daily subcutaneous (s.c.) injections of 900 nmol kg−1 MK-801 (n = 8 mice and n = 4 cages), 1800 nmol kg−1 MK-801 (n = 6 mice and n = 3 cages) or vehicle (isotonic saline, n = 7 mice and n = 3 cages) over 7 days. One mouse and cage were excluded from vehicle group due to the development of constipation. a, Schematic. b, Change in body weight. c, Daily food intake. d, Cumulative food intake. e, Change in fat mass. f, Change in lean mass. g-l, Treatment of C57BL/6 J DIO mice with once-daily s.c. injections of 200 nmol kg−1 MK-801 (n = 8 mice and n = 4 cages), 600 nmol kg−1 MK-801 (n = 7 mice and n = 4 cages) or vehicle (isotonic saline, n = 7 mice and n = 4 cages) for 7 days. g, Schematic. h, Change in body weight. i, Cumulative food intake. j, Change in rectal temperature in response to treatment on day 7. k, Area under curve (AUC) of j. l, Baseline rectal temperature on day 7. m-p, Treatment of C57BL/6 J DIO mice with once-daily s.c. injections of 50 µmol kg−1 memantine (n = 6 mice and n = 3 cages), 125 µmol kg−1 memantine (n = 6 mice and n = 3 cages) or vehicle (isotonic saline, n = 6 mice and n = 3 cages) over 7 days. m, Schematic. n, Change in body weight. o, Daily food intake. p, Cumulative food intake. Data analysed by one-way ANOVA, multiple comparison, Bonferroni post hoc test (e, f, k and l) and two-way repeated measures ANOVA to assess main effects of treatment (b, d, h-j, n and p). Data represents mean ± SEM; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Detailed statistics are in Supplementary Table 1. The diagrams in a, g and m were created using BioRender.