Fig. 4.

SLC25A47 is required for pyruvate-derived hepatic gluconeogenesis. (A) Fasting blood glucose levels (6 h) in Slc25a47^Alb-Cre mice and littermate controls at 7 wk of age on a regular chow diet and at 4 wk on a high-fat diet. Regular diet; n = 16 for Slc25a47^Alb-Cre, n = 10 for controls. High-fat diet; n = 6 for Slc25a47^Alb-Cre, n = 11 for controls. *P < 0.05, ***P < 0.001 by unpaired Student’s t test. (B) Glucose tolerance test in Slc25a47^Alb-Cre mice (n = 6) and littermate controls (n = 11) at 4 wk of high-fat diet. 6-h-fasted mice received glucose (2 g kg⁻¹ body weight, i.p.). Right: Area under the curve (AUC) of the data. ns, not significant. (C) Insulin tolerance test in Slc25a47^Alb-Cre mice (n = 7) and littermate controls (n = 11) at 4 wk of high-fat diet. 6-h-fasted mice received insulin (0.4 U kg⁻¹ body weight, i.p.). (D) Pyruvate tolerance test in Slc25a47^Alb-Cre mice (n = 6) and littermate controls (n = 11) on a high-fat diet for 3 wk. 16-h-fasted mice received pyruvate (2 g kg⁻¹ body weight, i.p.). (E) Pyruvate tolerance test in male Slc25a47^Alb-Cre mice (n = 16) and littermate controls (n = 10) on a regular chow diet. (F) Pyruvate tolerance test in female Slc25a47^Alb-Cre mice (n = 8) and littermate controls (n = 12) on a regular chow diet. (G) Schematic illustration of tracer experiments. Fasted mice on a regular chow diet were infused with indicated ¹³C-labeled tracers via the catheter. (H) Direct contribution of ¹³C-labeled tracers to glucose, lactate, and glycerol in (G). n = 6 for Slc25a47^Alb-Cre, n = 6 for controls. *P < 0.05 by unpaired Student’s t test. (I) The relative contribution of ¹³C-labeled lactate to circulating levels of glucose, pyruvate, and lactate in (G). **P < 0.01. B–F, P-value determined by two-way ANOVA followed by Fisher's least significant difference (LSD) test. AUC: *P < 0.05, **P < 0.01, ****P < 0.0001 by unpaired Student’s t test.