Fig. 8. Notch1 knockdown in IngWAT showed a superior rescue effect in SAKO mice compared with SAKI mice.

a, k Illustration of Notch1 knockdown in the IngWAT of SAKO (a) and SAKI (k) mice. b, l Notch1 was specifically knocked down in the IngWAT of SAKO (b) and SAKI (l) mice; n = 4 per group. c, m Body weights of NCD-fed SAKO mice (c) and HFD-fed SAKI mice (m); n = 4 per group. d, e, n, o GTT (d) and ITT (e) results of NCD-fed SAKO mice (n = 4 per group), as well as GTT (n) and ITT (o) results of HFD-fed SAKI mice (n = 4 per group). The area under the curve (AUC) values are shown in the right panel. f, g, p, q Serum TG and TC levels in the NCD-fed SAKO mice (f, g) and HFD-fed SAKI mice (p, q); n = 4 per group. h, r Lipolytic gene expression levels of IngWAT in the NCD-fed SAKO mice (h) and HFD-fed SAKI mice (r); n = 4 per group. i, s Thermogenic gene expression levels of IngWAT in the NCD-fed SAKO mice (i) and HFD-fed SAKI mice (s); n = 4 per group. j, t HE staining results and adipocyte size quantification of IngWAT in the NCD-fed SAKO mice (j) and HFD-fed SAKI mice (t). Representative images of HE staining results from three independent experiments are shown. Right panel, the quantitative results of the size of each adipocyte counted (j: shCtrl, n = 104 cells; shNotch1, n = 107 cells. t: shCtrl, n = 102 cells; shNotch1, n = 101 cells). Scale bar, 20 μm. Values are the fold induction of gene expression normalized to the housekeeping gene β-Actin (b, h, i, l, r, s). Data are expressed as the mean ± SEM. Statistical significance was assessed by unpaired two-sided Student’s t test (b, c, f–k, l, m, p–t) or two-way ANOVA followed by Bonferroni’s multiple comparisons test (d, e, n, o). The exact P values are shown in the figure. SAKO Slc35d3 adipocyte-specific knockout, SAKI Slc35d3 adipocyte-specific knock-in, IngWAT inguinal white adipose tissue, TG triglyceride, TC total cholesterol, NCD normal chow diet, HFD high-fat diet. Source data are provided as a Source Data file.