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

Summary Background  Obesity is a clinical feature of patients with Cushing's disease. Peroxisome proliferators-activated receptor (PPAR)γ is the master regulator of adipogenesis; however, the expression of PPARγ isoforms in the subcutaneous adipose tissue (SAT) of patients with Cushing's disease is unknown. Aim and methods  The expression of PPARγ1 and PPARγ2 was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence (PPARγ2 only) in SAT samples of 7 patients with untreated active Cushing's disease (CushingUNTR), 8 with Cushing's disease in remission (CushingREM) after pituitary adenomectomy, 15 normal lean subjects (ControlLEAN), and 15 obese patients (ControlOBE). Results  ControlLEAN had a higher degree of PPARγ1 than PPARγ2 (PPARγ2/PPARγ1 ratio, 0·55 ± 0·35). PPARγ2/PPARγ1 ratio decreased in CushingUNTR (0·10 ± 0·043, P < 0·03 vs. ControlLEAN and ControlOBE), because of either increased PPARγ1 or reduced PPARγ2 expression. PPARγ2/PPARγ1 ratio was 0·48 ± 0·07 in CushingREM patients (P < 0·04 vs. CushingUNTR, P < 0·03 vs. ControlOBE). PPARγ2/PPARγ1 ratio was higher in ControlOBE 0·90 ± 0·38 than in ControlLEAN (P < 0·005 vs. ControlLEAN, P < 0·03 vs. CushingREM, P < 0·009 vs. CushingUNTR). PPARγ2/PPARγ1 ratio was related to serum cortisol levels only in patients with Cushing'disease (r = 0·688, P < 0·02). Conclusions  CushingUNTR patients had an abnormal expression of PPARγ isoforms in SAT related to serum cortisol levels. Although further studies are necessary, it is conceivable that variations in the expression of PPARγ isoforms might have a role in the abnormal adipogenesis of patients with Cushing's disease.