Maura Agostini, Erik Schoenmakers, Junaid Beig, Louise Fairall, Istvan Szatmari, Odelia Rajanayagam, Frederick W Muskett, Claire Adams, A David Marais, Stephen O'Rahilly, Robert K Semple, Laszlo Nagy, Amit R Majithia, John W R Schwabe, Dirk J Blom, Rinki Murphy, Krishna Chatterjee, David B Savage
Loss-of-function mutations in PPARG cause familial partial lipodystrophy type 3 (FPLD3) and severe metabolic disease in many cases. Missense mutations in PPARG are present in ∼1:500 people. Whilst mutations are often binarily classified as 'benign' or 'deleterious', prospective functional classification of all missense PPARG variants suggests that their impact is graded. Furthermore, in testing novel mutations with both prototypic 'endogenous' (e.g. prostaglandin J2 (PGJ2)) and synthetic ligands (thiazolidinediones, tyrosine agonists), we observed that synthetic agonists selectively rescue function of some PPARγ mutants...
April 5, 2018: Diabetes