Fig. 5: Liver-specific Zfyve28 knockout improved insulin sensitivity and relevant indicators associated with insulin resistance in mice. | Nature Communications

Fig. 5: Liver-specific Zfyve28 knockout improved insulin sensitivity and relevant indicators associated with insulin resistance in mice.

From: ZFYVE28 mediates insulin resistance by promoting phosphorylated insulin receptor degradation via increasing late endosomes production

Fig. 5

a Schematic of the construction of liver-specific Zfyve28 knockout mice. b, d qPCR (b, n = 5 biologically independent samples per group) and western blotting results (d, representative results of three independent parallel experiments) showed specific knockout of Zfyve28 in liver tissues. c Control flox/flox mice and LKO mice showed no difference in total food intake when fed a HFD; n = 5 per group. e Body weight of LKO mice and flox/flox mice; n = 5 biologically independent mice per group. f, g GTT and ITT results showed that LKO mice exhibited better glucose tolerance (f) and insulin sensitivity (g); n = 5 biologically independent mice per group. h Representative gross images and HE staining results of livers from flox/flox mice and LKO mice; n = 5 biologically independent mice per group. Scale bar, 100 μm. i–m Western blot analysis (i) of hepatic protein levels in flox/flox mice and LKO mice. The quantification results (j–m) are shown; n = 3 biologically independent samples per group. n–q Liver weight (n), liver/body weight ratio (o), heart weight (p), and heart/body weight ratio (q) of flox/flox mice and LKO mice; n = 5 biologically independent samples per group. r–w The levels of serum TG (r), serum T-CHO (s), liver TG (t), liver T-CHO (u), heart TG (v) and heart T-CHO (w) in flox/flox mice and LKO mice; n = 5 biologically independent samples per group. x-y An increase in microcirculatory blood flow in the hearts of LKO mice was confirmed by laser Doppler blood flow measurements. Representative images (x) and quantification results of relative blood flow in five independent parallel experiments (y) are presented. Scale bar, 2 mm. z SBP and DBP were lower in LKO mice than in flox/flox mice; n = 5 biologically independent mice per group. LKO liver-specific knockout, SBP systolic blood pressure, DBP diastolic blood pressure, TG triglyceride, T-CHO total cholesterol. Data are shown as means ± SD, and P values are determined by unpaired two-tailed Student’s t-test (b, e, j–w, y, z) or two-way ANOVA with Fisher’s LSD post hoc multiple comparisons test (f, g). The exact P values are shown in the figure. Source data are provided as a Source Data file.

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