Fig. 5: Inhibition of LDHA activity abrogates the anti-obesity effect of PFKO.

A Schematic diagram of the Seahorse XF Assay test of the hypothalamus Arc. Created in BioRender. Chen, Z. (2024) https://BioRender.com/j97w406. B, C Seahorse metabolic analysis (ECAR) of hypothalamus Arc in Fam172A^L/L or PFKO mice. n = 4 mice per group. D Western blot analysis of LDHA and PDK1 in hypothalamus Arc of Fam172A^L/L or PFKO mice. n = 3 mice per group. E Intracellular lactate levels of hypothalamus Arc in Fam172A^L/L or PFKO mice. n = 8 mice per group. F, G Adult male Fam172a^L/L or PFKO mice were fed a chow diet, and were then placed cannula directed to lateral ventricle. After 2 wks of recovery, mice were switched from chow diet to HFD and were i.c.v. administered aCSF or oxamate every other day for 21 days (F), created in BioRender. Chen, Z. (2024) https://BioRender.com/j97w406. Body weight gain (G) was assessed. n = 8 (Fam12a^L/L, ICV aCSF) or 9 (PFKO, ICV OX) or 10 (PFKO, ICV aCSF) mice per group. H, I Fat mass (H) and lean mass (I) of treated mice were also assessed. n = 8 (Fam12a^L/L, ICV aCSF) or 9 (PFKO, ICV OX) or 9 (PFKO, ICV aCSF) mice per group. J Representative H&E staining images of mouse adipose tissues. Scale bars, 100 μm. K, L After oxamate treatment, the mice were subjected to the GTT (K). The AUC (L) of GTT is shown. n = 9 (Fam12a^L/L, ICV aCSF) or 8 (PFKO, ICV OX) or 9 (PFKO, ICV aCSF) mice per group. M Average food intake assessed during the treatment period. n = 8 mice per group. N, O Central administration of oxamate decreased oxygen consumption (VO2, N), and energy expenditure (EE, O) in PFKO mice. lbm, lean body mass. n = 6 mice per group. Data are presented as mean ± SEM. two-tailed Student’s t-test (C, E), one-way ANOVA with Turkey’s post hoc test (L, M, N, O), two-way ANOVA with Bonferroni’s post hoc test (G, H, I, K). Source data are provided as a Source Data file.