Figure 1

Metabolomic investigation of PPARδ and PPARγ activation in white adipose tissue from ob / ob mice. (a) Chromatogram of GC-MS analysis of the total fatty acid content of white adipose tissue from an ob/ob mouse treated with the PPARδ agonist. Key metabolites are labeled. (b) Partial least squares-discriminant analysis (PLS-DA) of the GC-MS chromatograms from white adipose tissue from control animals (filled squares; n = 8) or those treated with a PPARδ (filled circles; n = 8) (R²(X) = 32%, Q² = 69%). (c) PLS-DA of the GC-MS chromatograms from white adipose tissue from control animals (filled squares; n = 8) or those treated with the PPARγ agonist (diamonds; n = 8) (R²(X) = 32%, Q² = 74%). (d) Box whisker plots of key metabolic changes in total fatty acids in white adipose tissue following treatment with either the PPARδ agonist (n = 8) or PPARγ agonist (n = 8). Significant differences were measured by ANOVA followed by a Tukey post-hoc test. *P < 0.05; **P < 0.01; ***P < 0.005. (e) Plot of PLS-DA scores showing the clustering of DI-MS negative ionization mode mass spectra run in triplicate from the organic phase of white adipose extracts from ob/ob mice treated with a PPARδ agonist compared with control animals: PPARδ agonist-treated (filled circles; n = 8), control (filled squares; n = 8) (R²(X) = 72%, Q² = 58%). (f) Plot of PLS-DA scores showing the clustering of DI-MS positive ionization mode mass spectra run in triplicate from the organic phase of white adipose extracts from ob/ob mice treated with a PPARγ agonist compared with control animals: PPARγ agonist-treated (diamonds; n = 8), control (filled squares; n = 8) (R² = 89%, Q² = 95%). (g) Key metabolic changes detected by liquid chromatography-MS in blood serum from animals treated with either a PPARδ agonist (n = 8) or PPARγ agonist (n = 8) compared with wild-type controls (n = 8). The metabolite changes demonstrate a restructuring of specific lipid species, particularly phosphatidylcholines (PC) and triacylglycerols (TAG), within the circulating lipid pool of PPARδ and PPARγ agonist-treated mice. The TAG species increased in the PPARδ agonist-treated mice marked in red are decreased in the PPARγ agonist-treated mice marked in blue.