Extended Data Fig. 3: Supplementary metabolic phenotyping of GLP-1–MK-801.
From: GLP-1-directed NMDA receptor antagonism for obesity treatment
a-c, Treatment of DIO mice with once-daily s.c. injections of 100 nmol kg−1 MK-801 (n = 7 mice and n = 4 cages), 100 nmol kg−1 GLP-1 (n = 6 mice and n = 3 cages), 100 nmol kg−1, GLP-1–MK-801 (n = 6 mice and n = 3 cages), co-administration of 100 nmol kg−1 GLP-1 and 100 nmol kg−1 MK-801 (n = 6 mice and n = 3 cages) or vehicle (isotonic saline, n = 7 mice and n = 4 cages) for 14 days. a, Schematic. b, Change in body weight. c, Cumulative food intake. d-g and o-s, Treatment of DIO mice in metabolic cages with once-daily s.c. injections of 100 nmol kg−1 MK-801 (n = 7-8 mice), 100 nmol kg−1 GLP-1 (n = 8 mice), 100 nmol kg−1 GLP-1–MK-801 (n = 8 mice) or vehicle (isotonic saline, n = 8 mice) for 14 days. d, Schematic. e, Change in body weight. f, Change in fat mass. For MRI, two values were not registered from MK-801 group, two values were not registered from GLP-1 group and two values were not registered from GLP-1–MK-801 group due to MRI instrumental error. g, Change in lean mass. h-m, GLP-1–MK-801 corrects body weight and fat mass relative to age-matched chow-fed control mice. Treatment of DIO mice with once-daily s.c. injections of 100 nmol kg−1 GLP-1–MK-801 (n = 8 mice and n = 4 cages), 300 nmol kg−1 GLP-1–MK-801 (n = 8 mice and n = 4 cages) or vehicle (isotonic saline, n = 7 mice and n = 4 cages) in comparison with vehicle-treated age-matched chow-fed C57BL/6 J mice (n = 16 mice and n = 8-11 cages) for 14 days. Three double-housed cages with age-matched control animals were split on day 7 of the experiment due to fighting. One mouse was found dead in vehicle group. h, Schematic. i, Change in body weight. j, Body weight on day 14. k, Cumulative food intake. l, Fat mass on day 14. m, Lean mass on day 14. n, Total locomotor activity of mice from indirect calorimetry study in Fig. 1i–p. o, Energy expenditure. One mouse in MK-801 group excluded due to sensor related deviation. p, Regression-based analysis of energy expenditure relative to body weight on day 14. q, Respiratory exchange ratio (RER). r, Average respiratory exchange ratio. s, Total locomotor activity. Data analysed by one-way ANOVA, multiple comparison, Bonferroni post hoc test (f, g, j, l-n, r and s), two-way repeated measures ANOVA to assess main effects of treatment (b, c, e and k), and ANCOVA computed with calR using body weight as a covariate (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, d and h were created using BioRender.