Increased expression of TNF-alpha, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels.
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-alpha, 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-alpha, IL-6, and IL-8 was increased in AT of HALS subjects (P < 0.05), and both AT TNF-alpha mRNA and plasma TNF-alpha were negatively correlated to plasma adiponectin (P < 0.05). Finally, TNF-alpha 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.
Lihn
Aina S
AS
Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Tage Hansensgade 2, 8000 Aarhus C, Denmark. lihn@dadlnet.dk
Richelsen
Bjørn
B
Pedersen
Steen B
SB
Haugaard
Steen B
SB
Rathje
Gulla Søby
GS
Madsbad
Sten
S
Andersen
Ove
O
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy; D052242:Adiponectin; D000273:Adipose Tissue / Q000737:chemistry; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001823:Body Composition; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D015870:Gene Expression; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics*
D052242:Adiponectin; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D011506:Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol