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Am J Physiol Endocrinol Metab 286: E941-E949, 2004. First published January 28, 2004; doi:10.1152/ajpendo.00490.2003
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Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy

Jussi Sutinen,1,2,* Katja Kannisto,4 Elena Korsheninnikova,3 Rachel M. Fisher,4 Ewa Ehrenborg,4 Tuulikki Nyman,3 Antti Virkamäki,3 Tohru Funahashi,5 Yuji Matsuzawa,5 Hubert Vidal,6 Anders Hamsten,4 and Hannele Yki-Järvinen1,4

1Divisions of Diabetes and 2Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, FIN-00029 HUS, Helsinki; 3Minerva Research Institute, FIN-00250 Helsinki, Finland; 4Atherosclerosis Research Unit, Department of Medicine, King Gustaf V Research Institute, Karolinska Institutet, S-17176 Stockholm, Sweden; 5Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; and 6Faculte de Medecine R Laennec, Institut National de la Santé et de la Recherche Medicale, Unité 449, F-69370 Lyon, France

Submitted 31 October 2003 ; accepted in final form 23 January 2004

Highly active antiretroviral therapy (HAART) has improved the prognosis of human immunodeficiency virus (HIV)-infected patients but is associated with severe adverse events, such as lipodystrophy and insulin resistance. Rosiglitazone did not increase subcutaneous fat in patients with HAART-associated lipodystrophy (HAL) in a randomized, double-blind, placebo-controlled trial, although it attenuated insulin resistance and decreased liver fat content. The aim of this study was to examine effects of rosiglitazone on gene expression in subcutaneous adipose tissue in 30 patients with HAL. The mRNA concentrations in subcutaneous adipose tissue were measured using real-time PCR. Twenty-four-week treatment with rosiglitazone (8 mg/day) compared with placebo significantly increased the expression of adiponectin, peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}), and PPAR{gamma} coactivator 1 and decreased IL-6 expression. Expression of other genes involved in lipogenesis, fatty acid metabolism, or glucose transport, such as acyl-CoA synthase, adipocyte lipid-binding protein, CD45, fatty acid transport protein-1 and -4, GLUT1, GLUT4, keratinocyte lipid-binding protein, lipoprotein lipase, PPAR{delta}, and sterol regulatory element-binding protein-1c, remained unchanged. Rosiglitazone also significantly increased serum adiponectin concentration. The change in serum adiponectin concentration was inversely correlated with the change in fasting serum insulin concentration and liver fat content. In conclusion, rosiglitazone induced significant changes in gene expression in subcutaneous adipose tissue and ameliorated insulin resistance in patients with HAL. Increased expression of adiponectin might have mediated most of the favorable insulin-sensitizing effects of rosiglitazone in these patients.

human immunodeficiency virus; adiponectin; real-time polymerase chain reaction; liver fat


Address for reprint requests and other correspondence: J. Sutinen, Helsinki Univ. Central Hospital, PO Box 348, FIN-00029 HUS, Helsinki, Finland (E-mail: jussi.sutinen{at}hus.fi).




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