Transplantation of adipose tissue lacking PAI-1 improves glucose tolerance and attenuates cardiac metabolic abnormalities in high-fat diet-induced obesity

Figures

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  Figure 1.. Transplantation of subcutaneous adipose tissue from PAI-1KO mice improves glucose tolerance and insulin sensitivity. (a) Schematic timeline of scWAT transplantation model. (b) Body weight and fasting glucose level (c) in each group. (d) Insulin levels were measured by ELISA in each group. n = 4–6 per group. *P < 0.05 vs. WT transplanted and sham. (e, f) Glucose tolerance tests (GTTs) and AUC (area under the curve) in each group. n = 4–6 per group. *P < 0.05 vs. WT transplanted and sham. (g, h) Insulin tolerance tests (ITTs) and AUC in each group. n = 4–6 per group. Results are expressed as means ± SEM. Differences between experimental groups were analysed by one-way ANOVA. Significance of differences was set at P < 0.05. *P < 0.05 vs. WT transplanted and sham

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  Figure 2.. Transplantation of scWAT from PAI-1KO mice increases glucose uptake in cardiac muscle. (a) Transverse, coronal, and sagittal PET/CT images of mice through the liver, abdominal subcutaneous white adipose tissue, gastrocnemius muscle, and heart. (b) PET intensities were normalized to total positron emissions for each mouse and plotted against time. The liver, WAT, gastrocnemius muscle, and heart are presented. Bars are the means±SEM, p values were generated with ANOVA; n = 4-6/each group. (c-e). Cardiac tissue lysates were prepared and subjected to western blotting to detect GLUT1 (c), GLUT4 (d), and PAI-1 (e). Representative images of 3 independent experiments are shown. All graphs correspond to the blots above them and represent densitometric analyses of 3 independent experiments. Differences between experimental groups were analysed by one-way ANOVA.*P < 0.05 vs sham and WT-derived

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  Figure 3.. Transplantation of scWAT from PAI-1KO mice leads to alterations in cardiac muscle mRNA. (a) Volcano plot showing the differentially expressed genes in cardiac muscle due to transplanted PAI-1KO and WT scWAT. The negative log10-transformed p values are plotted against the average log2 fold changes in gene expression. Data for genes that were not classified as differentially expressed are plotted in grey (p > 0.05). Data for genes that are differentially expressed due to transplanted PAI-1KO scWAT (p < 0.05) with an absolute log2 fold change of less than 2 are plotted in green. Data for genes that are differentially expressed due to transplanted PAI-1KO scWAT (p ≤ 0.05) with an absolute log2 fold change of greater than or equal to 2 are plotted in red, and those with an absolute log2 fold change of less than or equal to −2 are plotted in blue. (b-d). The significantly upregulated GO terms of mitochondrial function for differentially expressed mRNAs, including biological process (b), cellular component (c), and molecular function (d). (e). The significantly downregulated GO terms of fatty acid oxidation for differentially expressed mRNAs. GO, gene ontology

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  Figure 4.. Transplantation of scWAT from PAI-1KO mice increases the NAD+/NADH ratio in cardiac muscle. The total intracellular NAD+/NADH ratio of heart tissues was measured from sham, WT, and PAI-1KO transplanted mice. Bars are the means±SEM; n = 6 mice per group. *P < 0.05 vs. WT transplanted and sham