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This Article Full Text Full Text (PDF) All Versions of this Article: 285/5/E1072    most recent 00206.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (64) Citing Articles via Google Scholar Google Scholar Articles by Lihn, A. S. Articles by Andersen, O. Search for Related Content PubMed PubMed Citation Articles by Lihn, A. S. Articles by Andersen, O.

Increased expression of TNF-, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels

¹Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital and Faculty of Health Sciences, Aarhus University, DK-8000 Aarhus C; and Departments of ²Internal Medicine and Endocrinology, ³Infectious Diseases, and ⁴Radiology, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark

Submitted 8 May 2003 ; accepted in final form 18 July 2003

Human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) is a side effect of highly active antiretroviral therapy of HIV-infected patients; however, the mechanism of the lipodystrophy and insulin resistance seen in this syndrome remains elusive. Adiponectin, an adipocyte-specific protein, is thought to play an important role in regulating insulin sensitivity. We investigated circulating levels and gene expression of adiponectin in subcutaneous abdominal adipose tissue (AT) from 18 HIV-infected patients with HALS compared with 18 HIV-infected patients without HALS. Implications of cytokines for adiponectin levels were investigated by determining circulating levels of TNF-, IL-6, and IL-8 as well as gene expression of these cytokines in AT. HALS patients exhibited 40% reduced plasma adiponectin levels (P < 0.05) compared with non-HALS subjects. Correspondingly, adiponectin mRNA levels in AT were reduced by >50% (P = 0.06). HALS patients were insulin resistant, and a positive correlation was found between plasma adiponectin and insulin sensitivity (r = 0.55, P < 0.01) and percent limb fat (r = 0.61, P < 0.01). AT mRNA of TNF-, IL-6, and IL-8 was increased in AT of HALS subjects (P < 0.05), and both AT TNF- mRNA and plasma TNF- were negatively correlated to plasma adiponectin (P < 0.05). Finally, TNF- was found in vitro to inhibit human AT adiponectin mRNA by 80% (P < 0.05). In conclusion, HALS patients have reduced levels of plasma adiponectin and adiponectin mRNA in AT. Increased cytokine mRNA in AT is hypothesized to exert an inhibitory effect on adiponectin gene expression and, consequently, to play a role in the reduced plasma adiponectin levels found in HALS patients.

human immunodeficiency virus-associated lipodystrophy syndrome; tumor necrosis factor-; interleukin-6; interleukin-8; cytokines; fat redistribution; insulin resistance

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