A study of fatty acid binding protein 4 in HIV-1 infection and in combination antiretroviral therapy-related metabolic disturbances and lipodystrophy.
OBJECTIVE
The aim of the study was to determine circulating levels of fatty acid binding protein 4 (FABP-4) in a cohort of HIV-1-infected patients treated with combination antiretroviral therapy (cART) and to investigate the relationships between FABP-4 levels and insulin resistance, dyslipidaemia, lipodystrophy and levels of proinflammatory adipocytokines in these patients.


METHODS
A total of 282 HIV-1-infected patients treated with stable cART for at least 1 year (132 with lipodystrophy and 150 without) and 185 uninfected controls (UCs) were included in the study. Anthropometric parameters were determined. Plasma levels of FABP-4, soluble tumour necrosis factor receptors 1 and 2 (sTNF-R1 and sTNF-R2), interleukin-18 (IL-18), IL-6, adiponectin and leptin were also analysed. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). Subcutaneous adipose tissue mRNA expression of proinflammatory cytokines was assessed in 38 patients (25 with lipodystrophy and 13 without) by real-time polymerase chain reaction (PCR).


RESULTS
The plasma FABP-4 concentration was significantly higher in patients with lipodystrophy than in those without (P=0.012). FABP-4 concentration was positively correlated with body mass index (BMI), HOMA-IR, and the concentrations of insulin, total cholesterol, triglycerides, sTNF-R1, leptin and IL-18, but showed a negative correlation with high-density lipoprotein (HDL) cholesterol and adiponectin concentrations. After adjusting for age, sex and BMI, the odds ratio (OR) for risk of lipodystrophy was found to be significantly increased for those with the highest levels of FABP-4 [OR 0.838, 95% confidence interval (CI) 0.435-1.616 for medium FABP-4 vs. OR 2.281, 95% CI 1.163-4.475 for high FABP-4]. In a stepwise regression model, FABP-4 was independently associated with HOMA-IR after controlling for clinical and inflammatory parameters (P=0.004). Moreover, a positive relationship was observed in patients with lipodystrophy between subcutaneous adipose tissue CD68 expression and FABP-4 plasma levels (r=0.525; P=0.031).


CONCLUSIONS
cART-treated HIV-1-infected patients with lipodystrophy have a systemic overproduction of FABP-4, which is closely linked to insulin resistance and inflammatory markers in subcutaneous adipose tissue.
Joan XXIII University Hospital of Tarragona, IISPV, Rovira i Virgili University, Tarragona, Spain.
X
X
Escoté
A
A
Megia
M
M
López-Dupla
M
M
Miranda
S
S
Veloso
V
V
Alba
P
P
Domingo
P
P
Pardo
C
C
Viladés
J
J
Peraire
M
M
Giralt
C
C
Richart
J
J
Vendrell
F
F
Vidal
D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000378:metabolism; D004359:Drug Therapy, Combination; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D052242:Adiponectin; D044966:Anti-Retroviral Agents; D008076:Cholesterol, HDL; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D020382:Interleukin-18; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha