Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy.
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 (PPARgamma), and PPARgamma 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, PPARdelta, 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.
Sutinen
Jussi
J
Division of Diabetes, Department of Medicine, Helsinki University Central Hospital, PO Box 348, FIN-00029 HUS, Helsinki, Finland. jussi.sutinen@hus.fi
Kannisto
Katja
K
Korsheninnikova
Elena
E
Fisher
Rachel M
RM
Ehrenborg
Ewa
E
Nyman
Tuulikki
T
Virkamäki
Antti
A
Funahashi
Tohru
T
Matsuzawa
Yuji
Y
Vidal
Hubert
H
Hamsten
Anders
A
Yki-Järvinen
Hannele
H
D052242:Adiponectin; D000273:Adipose Tissue / Q000187:drug effects* / Q000502:physiology; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001823:Body Composition; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D000077154:Rosiglitazone; D040521:Subcutaneous Tissue / Q000187:drug effects* / Q000502:physiology; D045162:Thiazolidinediones / Q000008:administration & dosage*
D052242:Adiponectin; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone