(a) Seahorse measurements (N=10 wells per condition) of the extracellular acidification rate (ECAR) and their corresponding metabolic rates in (b). N=30 wells (glycolysis) and N=29 wells (glycolytic capacity) per condition. (c) Abundance of glucokinase (Gck), phosphoglucomutase (Pgm), pyruvate kinase (Pklr) and pyruvate dehydrogenase complex (Pdha1, Pdhb) by proteomics after in vivo Rab24KD. N=6 animals per condition. (d) Glucose uptake assay under basal, oligomycin (2 μM), antimycin A (AA 1 μM) + rotenone (Rot 1 μM) and Glucose (25 mM) conditions. N=5 independent wells per condition. Relative expression of GLUT1 and GLUT2 in vitro (N=4 wells per condition) (e) and in livers of control and Rab24 KD mice (N=6 animals per condition) (f). (g) Lactate secretion in primary hepatocytes analyzed from N=8 (CTR) and N=9 (KD) independent wells. All in vitro experiments measured after 3 days after RNAi (40 nM) in primary hepatocytes. (h) ipPTT (2 g/kg) of control (N=5) and Rab24 KD (N=6) mice after 16 h of fasting. All animals treated with control (CTR) and Rab24 (KD) LNPs (0.5 mg/kg) (mean +/- SEM). *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, by two-tailed unpaired Student’s t-test. Only data that reached statistical significance are indicated.