Authors: He, G.¹; Andersen, O.²; Haugaard, S. B.²; Lihn, A. S.²; Pedersen, S. B.¹; Madsbad, S.²; Richelsen, B.

Source: European Journal of Clinical Investigation, Volume 35, Number 9, September 2005 , pp. 583-590(8)

Publisher: Wiley-Blackwell

Abstract:

Background

PAI-1, an important inhibitor of fibrinolysis, is increased in obese subjects and has been shown to be an independent risk factor for cardiovascular disease. In the present study, we investigated the association between circulating levels of PAI-1 and locally produced PAI-1 in adipose tissue and body fat distribution and adipokines (TNF-, TNF receptors, IL-6, IL-8) in patients with and without HIV-associated lipodystrophy syndrome (HALS). Materials and methods

Eighteen men with HALS and 18 men with HIV but without HALS were investigated. DEXA and computed tomography scan were performed to determine total body fat and visceral adipose tissue mass. Insulin sensitivity was determined by the euglycaemic clamp technique. Plasma levels of PAI-1 and cytokines were determined. In addition, PAI-1, TNF-, IL-6 and IL-8 mRNA levels in subcutaneous adipose tissue were measured by real-time reverse transcriptase polymerase chain reaction. Results

HALS patients were characterized by a 3-fold increased visceral adipose tissue (P < 0·001) and reduced limb fat (P < 0·01) as compared with non-HALS patients but with no difference in total fat mass between the groups. Plasma PAI-1 was increased in HALS patients (16·7 ng mL^-1 vs. 8·2 ng mL^-1, P < 0·05). Plasma PAI-1 was positively correlated with BMI (r = 0·74, P < 0·01), plasma TNF- level (r = 0·64, P < 0·01), sTNFR-I (r = 0·38, P < 0·05), and visceral fat (r = 0·67, P < 0·01). Moreover, plasma PAI-1 was negatively associated with insulin sensitivity (r = -0·57, P < 0·01) and the percentage of limb fat (r = -0·57, P < 0·01). A positive correlation was found between plasma PAI-1 and TNF- mRNA level. No association was, however, found between plasma PAI-1 and PAI-1 mRNA level in adipose tissue. Conclusion

Plasma PAI-1 is increased in HALS patients and it is suggested that dysregulation of the TNF-system (high TNF and high sTNFR1) may play a role in up-regulating PAI-1 in HALS.

Eur J Clin Invest 2005; 35 (9): 583 –590

Keywords: Adipose tissue; cytokines; human immunodeficiency virus (HIV); insulin resistance; lipodystrophy; plasminogen activator inhibitor type 1 (PAI-1)

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2362.2005.01547.x

Affiliations: 1: Aarhus University Hospital, Aarhus, Denmark and 2: Hvidovre University Hospital, Hvidovre, Denmark

Publication date: 2005-09-01

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