Alterations in thigh subcutaneous adipose tissue gene expression in protease inhibitor-based highly active antiretroviral therapy.
Use of protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) has been associated with altered regional fat distribution, insulin resistance, and dyslipidemias. To assess how PI-based HAART affects adipocyte gene expression in male HIV-1-infected patients, reverse transcription-polymerase chain reaction was used to quantify messenger RNA expression of adipocyte transcription factors and adipocytokines in thigh and abdominal subcutaneous adipose tissue from male (1) HIV-1 seronegative subjects (control, n = 9), (2) asymptomatic treatment-naive HIV-1-infected patients (naive, n = 6), (3) HIV-1-infected patients who were receiving antiretroviral agents but never received PIs (PI naive, n = 5), (4) HIV-1-infected patients who were receiving PI-based HAART (PI, n = 7), and (5) HIV-1-infected patients who discontinued the PI component of their antiviral therapy more than 6 months before enrollment (past PI, n =7). In the PI group, the messenger RNA expression levels of the CCAAT/enhancer-binding protein alpha , leptin, and adiponectin (18%, P < .01; 23%, P < .05; and 13%, P < .05, respectively) were significantly lower than the levels measured in the PI-naive group. These results are consistent with previous studies on the effects of PIs on cultured adipocytes. Prospective longitudinal studies of thigh fat adipose tissue gene expression could provide further insights on the pathogenesis of metabolic complications associated with PI-based HAART.
Chaparro
Juan
J
Departments of Medicine and Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Reeds
Dominic N
DN
Wen
Weidong
W
Xueping
E
E
Klein
Samuel
S
Semenkovich
Clay F
CF
Bae
Kyongtae T
KT
Quirk
Erin K
EK
Powderly
William G
WG
Yarasheski
Kevin E
KE
Li
Ellen
E
D000005:Abdomen; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018023:HIV Seronegativity; D015497:HIV-1; D006801:Humans; D008297:Male; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040521:Subcutaneous Tissue / Q000378:metabolism*; D013848:Thigh; D014157:Transcription Factors / Q000235:genetics
D016207:Cytokines; D011480:Protease Inhibitors; D012333:RNA, Messenger; D014157:Transcription Factors