PPAR Research / 2008 / Article / Fig 4

Review Article

The Development of INT131 as a Selective PPAR 𝜸 Modulator: Approach to a Safer Insulin Sensitizer

Figure 4

PPARγ full agonists, but not INT131, activate expression of a full agonist reporter gene, induce recruitment of DRIP205 coactivator peptide to PAPRγ, and cause lipid accumulation. (a) An expression construct bearing a PPAR response element designed to be activated by PPARγ full agonists was used to detect reporter gene expression. Transfected HEK cells were exposed to a range of concentrations of the indicated PPAR ligands, and expression measured. The maximal expression stimulated by INT131 was about 10% that promoted by rosiglitazone, pioglitazone, troglitazone, farglitazar, and BPx. (b) A homogenous time-resolved fluorescence energy transfer (FRET) assay was used to measure association of a DRIP205 coactivator peptide to PPARγ upon exposure to a range of concentrations of the indicated PPAR ligands. The maximal association stimulated by INT131 was about 20–25% that was promoted by rosiglitazone, pioglitazone, troglitazone, farglitazar, and netoglitazone. (c) Lipid accumulation was measured in murine preadipocytes exposed to a range of concentrations of the indicated PPAR ligands. The maximal lipid accumulation stimulated by INT131 was about 10% that was promoted by rosiglitazone, pioglitazone, troglitazone, farglitazar, and BPx, Data on file.
936906.fig.004a
(a)
936906.fig.004b
(b)
936906.fig.004c
(c)