The deficiency of PTP4A1 in mice fed a high-fat (HF) diet reduces glucose uptake by a decrease in GLUT2 on the plasma membrane in hepatocytes. (A) The assay of 2-deoxyglucose (2-DG) uptake in the livers, epididymal white adipose tissues (eWAT), and gastrocnemius muscles of wild-type (WT) and Ptp4a1-/- mice fed an HF diet for 12 weeks (n = 5). (B) FACS analysis after staining BODIPY on primary hepatocytes (PH) of WT and Ptp4a1-/- mice fed an HF diet. Data represent three independent experiments. (C) FACS analysis after staining glucose transporter 2 (GLUT2)-APC and asialoglycoprotein receptor 1 (ASGR1)-Alexa 488 on PH of WT and Ptp4a1-/- mice fed a normal chow (NC) or an HF diet. ASGR1 was used as a marker for hepatocytes. Data represent three independent experiments. (D) FACS analysis of the 2-NBDG glucose uptake assay on the PH of WT and Ptp4a1-/- mice fed an HF diet. Data represent three independent experiments. (E) FACS analysis after staining BODIPY on Hep3B expressing mock or PTP4A1 treated with bovine serum albumin-oleic acid (BSA-OA). Data represent three independent experiments. (F) The 2-NBDG uptake assay after incubation of BSA-OA on Hep3B transfected by PTP4A1-expressing vector or control vector. Representative images (left) and quantification for relative fluorescence intensity (RFI, right) (n = 4). Scale bar, 500 μm. Data are presented as the mean ± standard error of the mean. **P < 0.01, n.s., not significant (Mann-Whitney U test for A; two‐tailed Student's t‐test for F).