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, IL-6, and IL-8 in HIV-associated lipodystrophy. Implications for the reduced expression and plasma levels of adiponectin
1 Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Aarhus University Hospital, Aarhus C, Denmark
2 Depatment of Internal Medicine and Endocrinology, Hvidovre University Hospital, Hvidovre, Denmark
3 Department of Radiology, Hvidovre University Hospital, Hvidovre, Denmark
4 Department of Infectious Diseases, Hvidovre University Hospital, Hvidovre, Denmark
* To whom correspondence should be addressed. E-mail: lihn{at}dadlnet.dk.
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 to 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
to non-HALS. Correspondingly, adiponectin mRNA levels in AT were reduced by more than 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, HIV-infected patients with lipodystrophy 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 role for the reduced plasma adiponectin levels found in HALS patients.
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