HIV/antiretroviral therapy–related lipodystrophy syndrome (HALS) is associated with higher RBP4 and lower omentin in plasma

Abstract

Very little information is available on the involvement of newly characterized adipokines in human immunodeficiency virus (HIV)/antiretroviral therapy (ART)-associated lipodystrophy syndrome (HALS). Our aim was to determine whether apelin, apelin receptor, omentin, RBP4, vaspin and visfatin genetic variants and plasma levels are associated with HALS. We performed a cross-sectional multicentre study that involved 558 HIV type 1-infected patients treated with a stable highly active ART regimen, 240 of which had overt HALS and 318 who did not have HALS. Epidemiologic and clinical variables were determined. Polymorphisms in the apelin, omentin, RBP4, vaspin and visfatin genes were assessed by genotyping. Plasma apelin, apelin receptor, omentin, RBP4, vaspin and visfatin levels were determined by enzyme-linked immunosorbent assay in 163 patients (81 with HALS and 82 without HALS) from whom stored plasma samples were available. Student's t test, one-way ANOVA, chi-square test, Pearson and Spearman correlations and linear regression analysis were used for statistical analyses. There were no associations between the different polymorphisms assessed and the HALS phenotype. Circulating RBP4 was significantly higher (p < 0.001) and plasma omentin was significantly lower (p 0.001) in patients with HALS compared to those without HALS; differences in plasma levels of the remaining adipokines were nonsignificant between groups. Circulating RBP4 concentration was predicted independently by the presence of HALS. Apelin and apelin receptor levels were independently predicted by body mass index. Visfatin concentration was predicted independently by the presence of acquired immunodeficiency syndrome. HALS is associated with higher RBP4 and lower omentin in plasma. These two adipokines, particularly RBP4, may be a link between HIV/ART and fat redistribution syndromes.

HIV-1/HAART-Related Lipodystrophy Syndrome (HALS) Is Associated with Decreased Circulating sTWEAK Levels

“…Interestingly, we found a positive trend between levels of sTWEAK and levels of omentin, a recently identified insulin-sensitizing adipokine with TNFα inhibitory properties [ 38 , 39 ]. Omentin levels were reduced in HALS patients in this study and in our previous report[ 2 ]. This positive association may reinforce the beneficial effects of maintaining sTWEAK levels since low systemic levels of sTWEAK found in other settings, such as severe obesity and T2DM, are associated with an adverse effect on glucose uptake as a consequence of JNK1/2 activation by favoring TNFα signaling[ 11 ].…”

“…This was a multi-center, cross-sectional, case-control study comprising 120 adult treated HIV-1-infected patients, 64 without HALS and 56 with overt HALS. The patients were from a large cohort comprising 558 adult treated HIV-1-infected patients (318 without HALS and 240 with overt HALS) that has participated in our genetic and molecular studies of HALS pathogenesis[ 2 ]. In the present analysis, we used the 120 patients for whom stored serum and plasma samples, drawn at enrollment, were available.…”

“…This categorization was evaluated in the face, arms, legs, buttocks, abdomen, neck and breasts. The sum of the values corresponding to each body area indicated the degree of lipodystrophy: nil {0}, slight {1–6}, moderate {7–12} and severe {13–18} [ 2 – 4 , 31 – 32 ]. In the present study, we included only extreme lipodystrophy phenotypes (nil vs. severe cases) in order to avoid superposition between groups.…”

“…Several morphological and mechanistic events observed in HIV-1/Highly Active Antiretroviral Therapy (HAART)–associated lipodystrophy syndrome (HALS), an acquired form of lipodystrophy, are reminiscent of those seen in obesity[ 1 ]. This notion has been consistently demonstrated with respect to the disequilibrium of several adipokines/cytokines, such as leptin, adiponectin, resistin, RBP4, vaspin, visfatin and FABP4, among others[ 2 – 4 ].…”

Omentin-A Novel Adipokine in Respiratory Diseases

“…In contrast, other research groups demonstrated that the presence of nephritis was associated with elevated plasma omentin levels in patients with systemic lupus erythematosus (SLE) [ 48 ]. In addition, Peraire [ 49 ] demonstrated that human immunodeficiency virus/highly active anti-retroviral therapy (HIV/HAART)-associated lipodystrophy syndrome (HALS) was related to decreased omentin levels in plasma, indicating that omentin may be an important contact between HIV/HAART and fat redistribution syndromes. Furthermore, the circulating levels of omentin were significantly lower in painful temporo-mandibular disorders (TMD), which may be mediated by inflammatory pathways [ 50 ].…”