Submitted on February 11, 2008
Revised on April 8, 2008
Accepted on April 13, 2008
Adipose tissue inflammation and liver fat in patients with higly active antiretroviral therapy -associated lipodystrophy
Ksenia Sevastianova1*, Jussi Sutinen1, Katja Kannisto2, Anders Hamsten, Matti Ristola1, and Hannele Yki-Jarvinen3
1 Helsinki University Central Hospital
2 Karolinska Institutet
3 University of Helsinki
* To whom correspondence should be addressed. E-mail: ksenia.sevastianova{at}helsinki.fi.
In this cross-sectional study, we sought to determine whether gene expression of macrophage markers and inflammatory chemokines in lipoatrophic subcutaneous abdominal adipose tissue and liver fat content are increased and interrelated in human immunodeficiency virus (HIV)-1-positive, HAART-treated patients with lipodystrophy (HAART+LD+; n=27) compared to those without (HAART+LD-; n=13). The study groups were comparable with respect to age, gender and body mass index. The HAART+LD+ group had 2-fold more intra-abdominal (p=0.01) and 1.5-fold less subcutaneous fat (p=0.091) than the HAART+LD- group. As we have reported previously, liver fat was 10-fold higher in the HAART+LD+ as compared to the HAART+LD- group (p=0.00003). Inflammatory gene expression was increased in HAART-lipodystrophy: CD68 4.5-fold (p=0.000013), TNF
2-fold (p=0.0094), CCL2 2.5-fold (p=0.0024), CCL3 7-fold (p=0.0000017), ITGAM 3-fold (p=0.00067), EMR1 2.5-fold (p=0.0038) and ADAM8 3.5-fold (p=0.00057) higher in the HAART+LD+ as compared to the HAART+LD- group. mRNA concentration of CD68 (r=0.37, p=0.019), ITGAM (r=0.35, p=0.025), CCL2 (r=0.39, p=0.012) and CCL3 (r=0.54, p=0.0003) correlated with liver fat content. In conclusion, gene expression of markers of macrophage infiltration and adipose tissue inflammation is increased in lipoatrophic subcutaneous abdominal adipose tissue of patients with HAART-associated lipodystrophy compared to those without. CD68, ITGAM, CCL2 and CCL3 expression is significantly associated with accumulation of liver fat.
