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 PPARgamma isoforms in the subcutaneous adipose tissue (SAT) of patients with Cushing's disease is unknown.


OBJECTIVE
The expression of PPARgamma1 and PPARgamma2 was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence (PPARgamma2 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 PPARgamma1 than PPARgamma2 (PPARgamma2/PPARgamma1 ratio, 0.55 +/- 0.35). PPARgamma2/PPARgamma1 ratio decreased in Cushing(UNTR) (0.10 +/- 0.043, P < 0.03 vs. Control(LEAN) and Control(OBE)), because of either increased PPARgamma1 or reduced PPARgamma2 expression. PPARgamma2/PPARgamma1 ratio was 0.48 +/- 0.07 in Cushing(REM) patients (P < 0.04 vs. Cushing(UNTR), P < 0.03 vs. Control(OBE)). PPARgamma2/PPARgamma1 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)). PPARgamma2/PPARgamma1 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 PPARgamma isoforms in SAT related to serum cortisol levels. Although further studies are necessary, it is conceivable that variations in the expression of PPARgamma isoforms might have a role in the abnormal adipogenesis of patients with Cushing's disease.
Bogazzi
Fausto
F
Department of Endocrinology, University of Pisa, Italy. f.bogazzi@endoc.med.unipi.it
Ultimieri
Federica
F
Raggi
Francesco
F
Russo
Dania
D
Manetti
Luca
L
Cosci
Chiara
C
Sardella
Chiara
C
Costa
Aurelio
A
Santini
Ferruccio
F
Locci
Teresa
T
Bartalena
Luigi
L
Martino
Enio
E
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000601:surgery; D047495:PPAR gamma / Q000032:analysis* / Q000235:genetics; D047748:Pituitary ACTH Hypersecretion / Q000378:metabolism* / Q000601:surgery; D020033:Protein Isoforms / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D050151:Subcutaneous Fat / Q000737:chemistry*
D047495:PPAR gamma; D020033:Protein Isoforms; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone