Acute depletion of SLC25A47 improves glucose homeostasis independent of liver damage. (A) Schematic illustration of acute depletion of Slc25a47 study. Slc25a47flox/flox mice at 7 wk of age on a regular chow diet received AAV-Cre or AAV-null (control) via tail-vein. (B) Relative hepatic Slc25a47 mRNA levels of mice at 2 wk after AAV injection. n = 5 for both groups. *P < 0.05 by Mann–Whitney U test. (C) Body weight of mice in (B). *P < 0.05 by unpaired Student’s t test. (D) Serum FGF21 levels of mice after 2 wk of AAV injection. n = 16 for controls, n = 18 for AAV-Cre. ****P < 0.0001 by unpaired Student’s t test. (E) Relative expression of hepatic Fgf21 of mice in (B). **P < 0.01 by Mann–Whitney U test. (F) Fasting blood glucose levels (6 h) of mice in (B). ****P < 0.0001 by unpaired Student’s t test. (G) Fasting insulin levels of mice in (A). n = 16 for controls, n = 18 for AAV-Cre. *P < 0.05 by unpaired Student’s t test. (H) Pyruvate tolerance test at 2 wk after AAV injection. Fasted mice received pyruvate (2 g kg−1 body weight, i.p.). n = 15 for controls, n = 16 for AAV-Cre. P-value determined by two-way ANOVA followed by Fisher's LSD test. Right: AUC. **P < 0.01 by unpaired Student’s t test. (I) Insulin tolerance test in Slc25a47flox/flox mice at 6 wk. Fasted mice received insulin (0.4 U kg−1 body weight, i.p.). n = 11 for controls, n = 13 for AAV-Cre. Right: AUC. *P < 0.05 by unpaired Student’s t test. (J) Representative liver Picro-Sirius Red staining of mice in (B). Scale = 200 μm. (K) Relative liver expression of fibrosis marker genes of mice in (B). ns, not significant (L) Correlation between serum AST levels and hepatic Slc25a47 expression of mice in (B).