Rocchi, SPicard, FVamecq, JGelman, LPotier, NZeyer, DDubuquoy, LBac, PChampy, M FPlunket, K DLeesnitzer, L MBlanchard, S GDesreumaux, PMoras, DRenaud, J PAuwerx, J2009-04-022009-04-022009-04-02200110.1016/S1097-2765(01)00353-7https://infoscience.epfl.ch/handle/20.500.14299/3671611684010FMOC-L-Leucine (F-L-Leu) is a chemically distinct PPARgamma ligand. Two molecules of F-L-Leu bind to the ligand binding domain of a single PPARgamma molecule, making its mode of receptor interaction distinct from that of other nuclear receptor ligands. F-L-Leu induces a particular allosteric configuration of PPARgamma, resulting in differential cofactor recruitment and translating in distinct pharmacological properties. F-L-Leu activates PPARgamma with a lower potency, but a similar maximal efficacy, than rosiglitazone. The particular PPARgamma configuration induced by F-L-Leu leads to a modified pattern of target gene activation. F-L-Leu improves insulin sensitivity in normal, diet-induced glucose-intolerant, and in diabetic db/db mice, yet it has a lower adipogenic activity. These biological effects suggest that F-L-Leu is a selective PPARgamma modulator that activates some (insulin sensitization), but not all (adipogenesis), PPARgamma-signaling pathways.Thiazolidinedionestext::journal::journal article::research article