Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy.
OBJECTIVE
Adipocytokines, secreted by adipose tissue, may regulate fat metabolism, lipid and glucose homeostasis and insulin sensitivity. We analysed the relations between circulating concentrations of adiponectin, leptin, interleukin-6, tumor necrosis factor alpha and its soluble receptors sTNFR1 and R2, lipodystrophic phenotypes and metabolic alterations in patients under highly active antiretroviral therapy (HAART).


METHODS
We studied 131 consecutive HIV-infected males under protease inhibitor (PI)-based HAART, with body mass index < 27 kg/m2 and C-reactive protein (CRP) < 10 mg/l. Patients were classified in four groups according to clinical examination: no lipodystrophy (NL), lipohypertrophy (LH), lipoatrophy (LA) and mixed lipodystrophy (ML). In addition to adipocytokines, we measured plasma fasting levels of triglycerides, cholesterol, cardiovascular risk markers (high-sensitivity CRP and apolipoproteins B/A1 ratio), fasted and 2 h post-glucose loading glycemia and insulinemia and calculated the quantitative insulin sensitivity check index.


RESULTS
The patients were HIV-infected and PI-treated for a mean of 8.2 and 1.6 years respectively; 74% presented lipodystrophy, 38% altered glucose tolerance and 42% hypertriglyceridemia. Insulin sensitivity correlated positively with adiponectin and negatively with leptin and interleukin-6. Adiponectin, but not leptin, negatively correlated with all metabolic parameters. Insulin resistance, metabolic defects and cardiovascular risk markers were strongly negatively correlated with the adiponectin/leptin ratio (A/L), and positively with sTNFR1. LA patients had a longer duration of infection but ML patients presented the most severe metabolic alterations, insulin resistance and A/L decrease.


CONCLUSIONS
These results suggest that adiponectin and the TNFalpha system are related to lipodystrophy, insulin resistance and metabolic alterations in patients under PI-based HAART. A/L and sTNFR1 could predict insulin sensitivity and potential cardiovascular risk in these patients.
Vigouroux
Corinne
C
INSERM U.402, Faculté de Médecine Saint-Antoine, Paris, France.
Maachi
Mustapha
M
Nguyên
Thu-Huyen
TH
Coussieu
Christiane
C
Gharakhanian
Shahin
S
Funahashi
Tohru
T
Matsuzawa
Yuji
Y
Shimomura
Iichiro
I
Rozenbaum
Willy
W
Capeau
Jacqueline
J
Bastard
Jean-Philippe
JP
D052242:Adiponectin; D000273:Adipose Tissue / Q000276:immunology*; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D001054:Apolipoproteins A / Q000032:analysis; D001055:Apolipoproteins B / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood*; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D052242:Adiponectin; D019380:Anti-HIV Agents; D015703:Antigens, CD; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D020738:Leptin; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D002784:Cholesterol