a Construction strategy of SAKI mice. b qPCR analysis of Slc35d3 expression in different tissues from SAKI (n = 6) and WT (n = 7) mice. c Western blot analysis of Slc35d3 expression in different tissues from SAKI (n = 3) and WT (n = 3) mice. Right panel, summary of the quantification of three independent experiments. d SAKI and WT mice were fed an NCD from 4 to 8 weeks of age and then fed a HFD from 8 to 18 weeks. e Body weight curve of SAKI (n = 11) and WT (n = 11) mice fed a HFD (P = 0.009, 0.002, 0.004, 0.041, 0.00004, 0.002, 0.000008 for HFD-fed SAKI mice and controls from 4 to 10 weeks). f Body lengths of SAKI (n = 6) mice and WT mice (n = 6). g Representative images of fat pads from SAKI (n = 9) mice and controls (n = 9), as well as the tissue weights. h Serum lipid profiles (TG, TC and FFA) in SAKI (n = 9) mice and WT mice (n = 9). i, j Blood glucose concentrations during IP-GTT (i) and IP-ITT (j) in SAKI mice and their WT littermates; n = 5 per group. The area under the curve (AUC) values for GTT assays and ITT assays are shown. k–n Glucose infusion rates (k, l), whole-body insulin-stimulated glucose turnover (m) and 2-deoxyglucose uptake in IngWAT (n) during hyperinsulinemic–euglycemic clamps of HFD-fed SAKI (n = 5) and WT (n = 5) mice. Values are the fold induction of gene expression normalized to the housekeeping gene β-Actin (b, c). Data are expressed as the mean ± SEM. Statistical significance was assessed by unpaired two-sided Student’s t test (b, c, f–h, l–n) or two-way ANOVA followed by Bonferroni’s multiple comparisons test (e, i, j). The exact P values are shown in the figure or corresponding legends; *P < 0.05. EpiWAT epididymal white adipose tissue, BAT brown adipose tissue, IngWAT inguinal white adipose tissue, AsWAT anterior-subcutaneous white adipose tissue, TG triglyceride, TC total cholesterol, FFA free fatty acid, NCD normal chow diet, HFD high-fat diet, SAKI Slc35d3 adipocyte-specific knock-in. Source data are provided as a Source Data file.