Abnormal expression of PPAR gamma isoforms in the subcutaneous adipose tissue of patients with Cushing's disease

Background Obesity is a clinical feature of patients with Cushing's disease. Peroxisome proliferators-activated receptor (PPAR)gamma is the master regulator of adipogenesis; however, the expression of PPAR gamma isoforms in the subcutaneous adipose tissue (SAT) of patients with Cushing's disease is unknown. Aim and methods The expression of PPAR gamma 1 and PPAR gamma 2 was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence (PPAR gamma 2 only) in SAT samples of 7 patients with untreated active Cushing's disease (Cushing(UNTR)), 8 with Cushing's disease in remission (Cushing(REM)) after pituitary adenomectomy, 15 normal lean subjects (Control(LEAN)), and 15 obese patients (Control(OBE)). Results Control(LEAN) had a higher degree of PPAR gamma 1 than PPAR gamma 2 (PPAR gamma 2/PPAR gamma 1 ratio, 0.55 +/- 0.35). PPAR gamma 2/PPAR gamma 1 ratio decreased in Cushing(UNTR) (0.10 +/- 0.043, P < 0.03 vs. Control(LEAN) and Control(OBE)), because of either increased PPAR gamma 1 or reduced PPAR gamma 2 expression. PPAR gamma 2/PPAR gamma 1 ratio was 0.48 +/- 0.07 in Cushing(REM) patients (P < 0.04 vs. Cushing(UNTR), P < 0.03 vs. Control(OBE)). PPAR gamma 2/PPAR gamma 1 ratio was higher in Control(OBE) 0.90 +/- 0.38 than in Control(LEAN) (P < 0.005 vs. Control(LEAN), P < 0.03 vs. Cushing(REM), P < 0.009 vs. Cushing(UNTR)). PPAR gamma 2/PPAR gamma 1 ratio was related to serum cortisol levels only in patients with Cushing'disease (r = 0.688, P < 0.02). Conclusions Cushing(UNTR) patients had an abnormal expression of PPAR gamma isoforms in SAT related to serum cortisol levels. Although further studies are necessary, it is conceivable that variations in the expression of PPAR gamma isoforms might have a role in the abnormal adipogenesis of patients with Cushing's disease.