Home Search Abstracts Browse Sessions Program Committee View Session E-mail Abstract Author

 

 

Session 10 Oral Abstracts
Complications of Antiretroviral Therapy
Wednesday, 10 am - 12:30 pm
Presentation Time: 10:45 am
Auditorium


41
The Effect of Rosiglitazone on PPARg Expression in Human Adipose Tissue Is Limited by Continued Exposure to Thymidine NRTI
Patrick Mallon*1,2, R Sedwell1, G Rogers3, D Nolan4, P Unemori1, H Wand1, K Samaras5, A Kelleher1,2, S Emery1, D Cooper1,2, A Carr2, and The Rosey Investigators
1Natl Ctr in HIV Epidemiology and Clin Res, Univ of New South Wales, Sydney, Australia; 2St Vincent's Hosp, Sydney, Australia; 3Univ of Adelaide, Australia; 4Royal Perth Hosp, Australia; and 5Garvan Inst of Med Res, Sydney, Australia

Background:  Decreases in peroxisome proliferators-activated receptor gamma ( PPAR-g) expression in subcutaneous adipose tissue may be important in the pathogenesis of lipoatrophy. Despite this, rosiglitazone (RSG), a PPAR-g agonist, has not been shown to increase limb fat in lipoatrophic HIV-infected patients.

Methods:  We completed a sub-study of a randomized, placebo-controlled, 48-week trial examining the effect of RSG 4 mg twice daily on limb fat in 100 HIV-infected adults with lipoatrophy. We examined changes in mRNA expression in subcutaneous fat biopsies, performed at weeks 0, 2, and 48. RNA was extracted and real-time RT-PCR performed for mitochondrial and lipid metabolism genes, with results presented relative to b-actin expression, which did not change. Non-parametric analyses were applied.

Results:  We recruited 44 men (RSG n = 21, placebo n = 23) to this sub-study of which 21 were receiving the thymidine analogues (tNRTI) zidovudine (AZT) (n = 3) or stavudine (d4T) (n = 18) at baseline. Although groups were matched for baseline PPAR-g expression (p = 0.8), limb fat was lower in the RSG group (1.9 kg vs 2.3kg). Mitochondrial-encoded cytochrome-b expression was significantly lower in those treated with tNRTI (median 2.53 [IQR 4.45] vs 6.04 [4.54] for the no-tNRTI group, p = 0.001). At week 2, only those randomized to RSG in the no-tNRTI group experienced a significant rise in PPAR-g expression (p = 0.046). Similar significant increases in PPAR-g co-activator 1 (PGC-1) expression were also observed in the RSG no-tNRTI group. At week 48, PPAR-g expression was significantly higher only in the no-tNRTI group, regardless of randomized treatment allocation (p = 0.04), with RSG having no effect in the tNRTI group (see the table). No significant correlations were observed between changes in PPAR-g or PGC-1 expression and change in limb fat.

 

 

                                               PPARg

 

Week 2

Week 48

 

tNRTI

no tNRTI

tNRTI

no tNRTI

RSG

12 [99]

68 [56]

–22 [154]

87 [166]

Placebo

2 [97]

7 [173]

–32 [131]

74 [181]

 

                                               PGC-1

RSG

13 [69]

149 [341]

29 [63]

672 [976]

Placebo

35 [131]

107 [181]

119 [118]

313 [220]

Keywords: Lipodystrophy; Rosiglitazone; Mitochondrial toxicity