Adipose tissue inflammation and liver fat in patients with highly active antiretroviral therapy-associated lipodystrophy

Am J Physiol Endocrinol Metab. 2008 Jul;295(1):E85-91. doi: 10.1152/ajpendo.90224.2008. Epub 2008 Apr 22.

Abstract

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, highly active antiretroviral therapy (HAART)-treated patients with lipodystrophy (HAART+LD+; n = 27) compared with 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 twofold more intra-abdominal (P = 0.01) and 1.5-fold less subcutaneous (P = 0.091) fat than the HAART+LD- group. As we have reported previously, liver fat was 10-fold higher in the HAART+LD+ compared with the HAART+LD- group (P = 0.00003). Inflammatory gene expression was increased in HAART-lipodystrophy: CD68 4.5-fold (P = 0.000013), tumor necrosis factor (TNF)-alpha 2-fold (P = 0.0094), chemokine (C-C motif) ligand (CCL) 2 2.5-fold (P = 0.0024), CCL3 7-fold (P = 0.0000017), integrin alphaM (ITGAM) 3-fold (P = 0.00067), epidermal growth factor-like module containing, mucin-like, hormone receptor-like (EMR)1 2.5-fold (P = 0.0038), and a disintegrin and metalloproteinase domain (ADAM)8 3.5-fold (P = 0.00057) higher in the HAART+LD+ compared with 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 with those without. CD68, ITGAM, CCL2, and CCL3 expression is significantly associated with accumulation of liver fat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / immunology
  • Adipose Tissue / pathology*
  • Adult
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Body Composition / drug effects
  • Body Composition / immunology
  • Chemokines / biosynthesis
  • Chemokines / blood
  • Chemokines / genetics
  • Cross-Sectional Studies
  • Cytokines / biosynthesis
  • Cytokines / blood
  • Cytokines / genetics
  • Female
  • Gene Expression
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / pathology
  • HIV-1*
  • HIV-Associated Lipodystrophy Syndrome / genetics
  • HIV-Associated Lipodystrophy Syndrome / immunology
  • HIV-Associated Lipodystrophy Syndrome / pathology*
  • HIV-Associated Lipodystrophy Syndrome / virology
  • Humans
  • Inflammation / chemically induced
  • Inflammation / immunology
  • Inflammation / pathology
  • Liver / drug effects
  • Liver / immunology
  • Liver / metabolism*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Male
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics

Substances

  • Chemokines
  • Cytokines
  • RNA, Messenger