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Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy.
Am J Physiol Endocrinol Metab. 2004 Jun; 286(6):E941-9.AJ

Abstract

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.

Authors+Show Affiliations

Division of Diabetes, Department of Medicine, Helsinki University Central Hospital, PO Box 348, FIN-00029 HUS, Helsinki, Finland. jussi.sutinen@hus.fiNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14749206

Citation

Sutinen, Jussi, et al. "Effects of Rosiglitazone On Gene Expression in Subcutaneous Adipose Tissue in Highly Active Antiretroviral Therapy-associated Lipodystrophy." American Journal of Physiology. Endocrinology and Metabolism, vol. 286, no. 6, 2004, pp. E941-9.
Sutinen J, Kannisto K, Korsheninnikova E, et al. Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy. Am J Physiol Endocrinol Metab. 2004;286(6):E941-9.
Sutinen, J., Kannisto, K., Korsheninnikova, E., Fisher, R. M., Ehrenborg, E., Nyman, T., Virkamäki, A., Funahashi, T., Matsuzawa, Y., Vidal, H., Hamsten, A., & Yki-Järvinen, H. (2004). Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy. American Journal of Physiology. Endocrinology and Metabolism, 286(6), E941-9.
Sutinen J, et al. Effects of Rosiglitazone On Gene Expression in Subcutaneous Adipose Tissue in Highly Active Antiretroviral Therapy-associated Lipodystrophy. Am J Physiol Endocrinol Metab. 2004;286(6):E941-9. PubMed PMID: 14749206.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy. AU - Sutinen,Jussi, AU - Kannisto,Katja, AU - Korsheninnikova,Elena, AU - Fisher,Rachel M, AU - Ehrenborg,Ewa, AU - Nyman,Tuulikki, AU - Virkamäki,Antti, AU - Funahashi,Tohru, AU - Matsuzawa,Yuji, AU - Vidal,Hubert, AU - Hamsten,Anders, AU - Yki-Järvinen,Hannele, Y1 - 2004/01/28/ PY - 2004/1/30/pubmed PY - 2004/6/26/medline PY - 2004/1/30/entrez SP - E941 EP - 9 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 286 IS - 6 N2 - 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. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/14749206/Effects_of_rosiglitazone_on_gene_expression_in_subcutaneous_adipose_tissue_in_highly_active_antiretroviral_therapy_associated_lipodystrophy_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00490.2003?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -