A unique PPARgamma ligand with potent insulin-sensitizing yet weak adipogenic activity.

Abstract:

:FMOC-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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Rocchi S,Picard F,Vamecq J,Gelman L,Potier N,Zeyer D,Dubuquoy L,Bac P,Champy MF,Plunket KD,Leesnitzer LM,Blanchard SG,Desreumaux P,Moras D,Renaud JP,Auwerx J

doi

10.1016/s1097-2765(01)00353-7

subject

Has Abstract

pub_date

2001-10-01 00:00:00

pages

737-47

issue

4

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(01)00353-7

journal_volume

8

pub_type

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